Effects of anemia and blood transfusion on clot formation and platelet function in patients with septic shock: a substudy of the randomized TRISS trial

Transfusion ◽  
2018 ◽  
Vol 58 (12) ◽  
pp. 2807-2818 ◽  
Author(s):  
Lene Russell ◽  
Lars Broksø Holst ◽  
Theis Lange ◽  
Xuan Liang ◽  
Sisse Rye Ostrowski ◽  
...  
Keyword(s):  
Septic Shock ◽  
Blood Transfusion ◽  
Platelet Function ◽  
Clot Formation

Properties of Fibrinogen Cleaved by Jararhagin, a Metalloproteinase from the Venom of Bothrops jararaca

1994 ◽  
Vol 72 (02) ◽  
pp. 244-249 ◽  
Author(s):  
Aura S Kamiguti ◽  
Joseph R Slupsky ◽  
Mirko Zuzel ◽  
Charles R M Hay
Keyword(s):  
Platelet Aggregation ◽  
Platelet Function ◽  
Fibrin Clot ◽  
Clot Formation ◽  
Human Fibrinogen ◽  
Activated Platelets ◽  
Bothrops Jararaca ◽  
Platelet Binding ◽  
Fibrin Monomers ◽  
Fibrinogen Molecule

SummaryHaemorrhagic metalloproteinases from Bothrops jararaca and other venoms degrade vessel-wall and plasma proteins involved in platelet plug and fibrin clot formation. These enzymes also cause proteolytic digestion of fibrinogen which has been suggested to cause defective platelet function. Fibrinogen degradation by jararhagin, a metalloproteinase from B. jararaca, and the effect of jararhagin fibrinogenolysis on both platelet aggregation and fibrin clot formation were investigated. Jararhagin was found to cleave human fibrinogen in the C-terminal region of the Aα-chain giving rise to a 285-290 kDa fibrinogen molecule lacking the Aα-chain RGD 572-574 platelet-binding site. Platelet binding and aggregation of ADP-activated platelets is unaffected by this modification. This indicates that the lost site is not essential for platelet aggregation, and that the remaining platelet binding sites located in the N-terminal portion of Aα chains (RGD 95-97) and the C-terminal of γ chains (dodecapeptide 400-411) are unaffected by jararhagin-digestion of fibrinogen. Fibrin clot formation with thrombin of this remnant fibrinogen molecule was defective, with poor polymerization of fibrin monomers but normal release of FPA. The abnormal polymerization could be explained by the loss of one of the two complementary polymerization sites required for side-by-side association of fibrin protofibrils. Jararhagin-induced inhibition of platelet function, an important cause of haemorrhage in envenomed patients, is not caused by proteolysis of fibrinogen, as had been thought, and the mechanism remains to be elucidated.

scholarly journals Platelet transfusion improves clot formation and platelet function in severely thrombocytopenic haematology patients

2021 ◽  
Author(s):  
Cecilia Karlström ◽  
Gunilla Gryfelt ◽  
Laurent Schmied ◽  
Stephan Meinke ◽  
Petter Höglund
Keyword(s):  
Platelet Function ◽  
Platelet Transfusion ◽  
Clot Formation ◽  
Haematology Patients

Influence of Nanopolymers with Different End-Functionalities on Platelet Function and the Coagulation Cascade - An Ex-Vivo Study.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 4038-4038
Author(s):  
Meera Chitlur ◽  
Erin Ware ◽  
Sujata Kannan ◽  
Wendy Hollon ◽  
Steve Buck ◽  
...  
Keyword(s):  
Flow Cytometry ◽  
Platelet Aggregation ◽  
Surface Charge ◽  
Platelet Function ◽  
Whole Blood ◽  
Clot Formation ◽  
Coagulation Cascade ◽  
Cancer Drug ◽  
Dendritic Polymers ◽  
Drug Concentrations

Abstract Dendritic polymers are branched nanopolymers with a central core and multiple peripheral functional groups that offer great potential as high payload delivery vehicles carrying multiple copies of drug molecules, targeting ligands and imaging agents to their site of action. Their nanoscopic dimensions offer exciting possibilities for achieving high intracellular drug concentrations in many therapeutic areas including anti-cancer drug delivery. Biocompatibility and biodistribution of dendritic polymers may be influenced by surface charge and concentration. One of the major challenges in their use is the effect on coagulation. The objective of this study was to determine the effect of change in surface charge and concentration of dendritic polymer on cellular and enzymatic components of coagulation. Materials and Methods: The effect of increasing concentrations (1, 10, 100, and 1000mcg/ml) of polyamidoamine (PAMAM) dendrimers with -COOH (anionic), -OH (neutral), and -NH2 (cationic) end functionalities, on platelet function and coagulation was evaluated using thromboelastography, whole blood aggregation, and flow cytometry. The thromboelastographic profile and platelet aggregation studies were obtained on samples of whole blood incubated for thirty minutes with dendrimer. Platelets were incubated with FITC labelled dendrimer for 30,60 and 120 mins, to determine uptake and platelet activation using flow cytometry. All tests were performed in triplicate. RESULTS: Thromboelastography: No significant effect on clot formation (time to clot formation and size) was seen with PAMAM-COOH (COOH) or PAMAM-OH (OH). Prolonged time to initiation of clot and decreased size were noted with 100 and 1000mcg/ml of PAMAM-NH2(NH2) as shown in figure1, indicating impairment of both the enzymatic and cellular components of the coagulation system. Whole Blood Aggregation: Neither platelet aggregation nor secretion were significantly affected by COOH or OH. Platelet aggregation was significantly decreased with NH2 at 100 and 1000mcg/ml. Flow Cytometry: Spontaneous CD62 activation was seen in platelets incubated with NH2. No spontaneous CD62 activation was noted with COOH or OH even at 1000mcg/ml. Platelet uptake of FITC labeled dendrimer was assessed at 30, 60 and 120mins of incubation. Increased uptake of FITC labeled dendrimer was noted at 2 hours with NH2. TEG clotting Profiles with PAMAM-NH2. TEG clotting Profiles with PAMAM-NH2. CONCLUSIONS: Surface charge of the dendritic nanopolymers plays a significant role on its effect on coagulation and platelet function. The anionic -COOH terminated and neutral -OH terminated dendrimers had no effect on hemostasis even at the highest concentrations while the cationic-NH2 was associated with inhibition of platelet aggregation and delayed clot initiation at higher concentrations. This would indicate that the anionic and neutral dendrimers would serve as better vehicles than cationic dendrimers for targeted delivery of therapeutic agents.

Autologous Blood Transfusion for Cardiopulmonary Bypass: Effects of Storage Conditions on Platelet Function

2006 ◽  
Vol 20 (4) ◽  
pp. 541-547 ◽  
Author(s):  
Ian R. Ramnarine ◽  
Michael J. Higgins ◽  
Anne McGarrity ◽  
Zahid Mahmood ◽  
David J. Wheatley ◽  
...  
Keyword(s):  
Cardiopulmonary Bypass ◽  
Blood Transfusion ◽  
Platelet Function ◽  
Autologous Blood ◽  
Storage Conditions ◽  
Autologous Blood Transfusion

Haematological emergencies

2018 ◽  
Author(s):  
Drew Provan ◽  
Trevor Baglin ◽  
Inderjeet Dokal ◽  
Johannes de Vos ◽  
Hassan Al-Sader
Keyword(s):  
Septic Shock ◽  
Blood Transfusion ◽  
Thrombolytic Therapy ◽  
Thrombotic Thrombocytopenic Purpura ◽  
Disseminated Intravascular Coagulation ◽  
Transfusion Reaction ◽  
Thrombocytopenic Purpura ◽  
Heparin Induced Thrombocytopenia ◽  
Massive Blood Transfusion ◽  
Transfusion Reactions

Septic shock/neutropenic fever - Acute transfusion reactions - Delayed transfusion reaction - Post-transfusion purpura - Hypercalcaemia - Hyperviscosity - Disseminated intravascular coagulation - Overdosage of thrombolytic therapy - Heparin overdosage - Heparin-induced thrombocytopenia - Warfarin overdosage - Massive blood transfusion - Paraparesis/spinal collapse - Leucostasis - Thrombotic thrombocytopenic purpura - Sickle crisis

scholarly journals TEG®6s system measures the contributions of both platelet count and platelet function to clot formation at the site-of-care

Platelets ◽  
2019 ◽  
Vol 31 (7) ◽  
pp. 932-938
Author(s):  
Joao D. Dias ◽  
Carlos G Lopez-Espina ◽  
Kevin Bliden ◽  
Paul Gurbel ◽  
Jan Hartmann ◽  
...  
Keyword(s):  
Platelet Count ◽  
Platelet Function ◽  
Clot Formation

Effect of blood transfusion on oxygen consumption in pediatric septic shock

1990 ◽  
Vol 18 (10) ◽  
pp. 1087-1091 ◽  
Author(s):  
RICHARD B. MINK ◽  
MURRAY M. POLLACK
Keyword(s):  
Septic Shock ◽  
Oxygen Consumption ◽  
Blood Transfusion

Dysfunctional Endothelium Drives a Pre-DIC State in Endotoxemia

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 3725-3725 ◽  
Author(s):  
Karen E.P. De Ceunynck ◽  
Sarah J. Higgins ◽  
Sharjeel A. Chaudhry ◽  
Samir Parikh ◽  
Robert C. Flaumenhaft
Keyword(s):  
Endothelial Dysfunction ◽  
Platelet Function ◽  
Time Course ◽  
Conflicts Of Interest ◽  
Thrombus Formation ◽  
Endothelial Activation ◽  
Clot Formation ◽  
Microvascular Endothelium ◽  
Coagulation Parameters ◽  
Laser Injury

Abstract Uncontrolled pro-coagulant responses in sepsis can lead to disseminated intravascular coagulation (DIC), a complication associated with markedly increased mortality. Abnormalities of coagulation, fibrinolysis, and platelet function can lead to both microvascular thrombosis contributing to multi-organ dysfunction syndrome or hemorrhagic complications. To understand the inciting causes of DIC in sepsis, we first evaluated the time course of platelet function, coagulation parameters and markers of endothelial activation following LPS exposure. These studies demonstrated that endothelial dysfunction preceded derangement of platelet function or coagulation parameters. To evaluate the thrombotic response of the endothelium early in endotoxemia, we injured the microvascular endothelium of cremaster arterioles of mice using a laser 1-3 hours following LPS exposure. Platelet and fibrin formation at sites of injury were significantly increased following LPS exposure to respectively 190% (p=0.026) and 195% (p<0.001) of control values. No significant differences were observed in platelet counts, platelet function (aggregation and activation) or coagulation parameters (PT) in mice treated with LPS for 3 hours compared to vehicle controls. Plasma levels of the endothelial markers VWF, soluble VCAM and E-selectin, however, were significantly increased following LPS exposure, demonstrating early endothelial activation. Furthermore, even when platelet accumulation was inhibited using the anti-platelet drug eptifibatide, fibrin generation at sites of laser injury was still significantly (p<0.01) increased in LPS-treated mice. Together, these data show that endothelial activation precedes disruption of platelets and coagulation in endotoxemia. Endothelial dysfunction is associated with perturbation of the endothelial Ang1/Tie2 pathway, characterized by significantly reduced Tie2 function and Ang1 levels. Therefore, we assessed thrombus formation in Tie2+/- mice in the absence of LPS. Fibrin generation at sites of laser injury was significantly increased in Tie2+/- mice to 192% of littermate (Tie2+/+) controls (p<0.01). As loss of Tie2 mimics the LPS-induced phenotype, we next determined whether activation of the Tie2 pathway could reduce fibrin clot formation. Ang1 stimulates phosphorylation of Tie2, promoting protective signaling in endothelium. To determine whether the pro-thrombotic consequences of endotoxemia on Tie2 signaling could be reversed using Ang1, mice were injected with adenovirus expressing Ang1 or control adenovirus prior to LPS exposure. Dephoshorylation of Tie2 associated due to LPS exposure was reduced with Ang1-treatment. In our in vivo thrombosis model, Ang1 inhibited the increased fibrin accumulation at sites of laser injury in endotoxemic mice to baseline levels. Tail snip assays showed that even though elevated Ang1 levels normalized LPS-induced augmentation of thrombus formation, increased Ang1 did not affect bleeding times. These data indicate that Ang1 stimulation of Tie2 signaling can regulate pathologic clot formation in the setting of inflammation without bleeding risk. Together, our studies show that endothelial dysfunction drives a pre-DIC state in endotoxemia. Targeting these early endothelial responses might represent an novel approach for reducing thrombosis in sepsis without enhancing bleeding risks. Future studies will evaluate the mechanism involved. Disclosures No relevant conflicts of interest to declare.

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