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

Author(s):  
Cecilia Karlström ◽  
Gunilla Gryfelt ◽  
Laurent Schmied ◽  
Stephan Meinke ◽  
Petter Höglund
1994 ◽  
Vol 72 (02) ◽  
pp. 244-249 ◽  
Author(s):  
Aura S Kamiguti ◽  
Joseph R Slupsky ◽  
Mirko Zuzel ◽  
Charles R M Hay

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.


Transfusion ◽  
2018 ◽  
Vol 58 (12) ◽  
pp. 2807-2818 ◽  
Author(s):  
Lene Russell ◽  
Lars Broksø Holst ◽  
Theis Lange ◽  
Xuan Liang ◽  
Sisse Rye Ostrowski ◽  
...  

2021 ◽  
Vol 167 (3) ◽  
pp. e1.5-e1
Author(s):  
Tom Scorer ◽  
Andrew Mumford

IntroductionPlatelet dysfunction (thrombocytopathy) is a major problem in the bleeding patient and increases morbidity and healthcare costs. The thrombocytopathy resulting from cardiopulmonary bypass (CPB) can be used to study therapies targeted to improve outcomes in other scenarios, such as trauma. Platelet transfusion is used widely to correct thrombocytopathy. However, the current standard, room temperature stored platelets (RTP) have several disadvantages including; short shelf life, risk of bacterial contamination and deterioration in platelet function during storage. Cold stored platelets (CSP) are a potential alternative product with longer shelf life, reduced contamination risk and better-preserved platelet function.MethodsUsing ex vivo mixing studies, we investigated whether CSP were better able to reverse the thrombocytopathy associated with cardiac surgery than RTP. Blood samples were collected from 20 cardiac surgery patients. Donor platelets were split into two bags and stored at either 4°C (CSP), or 22°C (RTP) for up to seven days. The donor platelets were mixed with the patient blood samples to simulate platelet transfusion. The mixed samples were analysed using the TEG 5000 and using a collagen coated flow chamber at arterial shear. Patient samples were analysed alongside healthy controls (n = 20).ResultsAfter mixing the patient samples with CSP, the TEG R times were shorter than in samples mixed with RTP (p<0.0001), indicating more rapid initiation of clot formation. In the flow chamber experiments, the clot volume was greater in the patient samples mixed with CSP compared with samples mixed with RTP (p<0.0001).ConclusionsThese findings suggest that CSP, but not RTP can partially reverse the thrombocytopathy associated with cardiac surgery ex vivo, at clinically relevant mixing volumes. Reversal of thrombocytopathy by mixing CSP was greatest in the arterial shear model, which may indicate superior in vivo efficacy that requires confirmation in clinical trials.* this abstract presentation was awarded First Place.


Author(s):  
Lihui Wang ◽  
Oswaldo Valencia ◽  
Simon Phillips ◽  
Vivek Sharma

Abstract Background Platelet dysfunction is a common cause of bleeding, perioperative blood transfusion, and surgical re-exploration in cardiac surgical patients. We evaluated the effect of incorporating a platelet function analyzer utilizing impedance aggregometry (Multiplate, Roche, Munich, Germany) into our local transfusion algorithm on the rate of platelet transfusion and postoperative blood loss in patients undergoing coronary artery bypass grafting (CABG) surgery. Methods Data were collected on patients undergoing CABG surgery from January 2015 to April 2017. Patients who underwent surgery before and after introduction of this algorithm were classified into prealgorithm and postalgorithm groups, respectively. The primary outcome was the rate of platelet transfusion before and after implementation of the Multiplate-based transfusion algorithm. Secondary outcomes included transfusion rate of packed red blood cells, postoperative blood loss at 12 and 24 hours, length of stay in the intensive care unit, and the hospital and mortality. Results A total of 726 patients were included in this analysis with 360 and 366 patients in the pre- and postalgorithm groups, respectively. Transfusion rates of platelets (p = 0.01) and packed red blood cells (p = 0.0004) were significantly lower following introduction of the algorithm in patients (n = 257) who had insufficient time to withhold antiplatelet agents. Receiver operating characteristic curves defined optimal cutoff points of arachidonic acid and adenosine diphosphate assays on the Multiplate to predict future platelet transfusion were 23AU and 43AU, respectively. Conclusions The introduction of a Multiplate-based platelet transfusion algorithm showed a statistically significant reduction in the administration of platelets to patients undergoing urgent CABG surgery.


Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 4038-4038
Author(s):  
Meera Chitlur ◽  
Erin Ware ◽  
Sujata Kannan ◽  
Wendy Hollon ◽  
Steve Buck ◽  
...  

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.


Author(s):  
Binggang Xiang ◽  
Guoying Zhang ◽  
Yan Zhang ◽  
Congqing Wu ◽  
Smita Joshi ◽  
...  

Objective: Platelet transfusion is a life-saving therapy to prevent or treat bleeding in patients with thrombocytopenia or platelet dysfunction. However, for >6 decades, safe and effective strategies for platelet storage have been an impediment to widespread use of platelet transfusion. Refrigerated platelets are cleared rapidly from circulation, precluding cold storage of platelets for transfusion. Consequently, platelets are stored at room temperature with an upper limit of 5 days due to risks of bacterial contamination and loss of platelet function. This practice severely limits platelet availability for transfusion. This study is to identify the mechanism of platelet clearance after cold storage and develop a method for platelet cold storage. Approach and Results: We found that rapid clearance of cold-stored platelets was largely due to integrin activation and apoptosis. Deficiency of integrin β3 or caspase-3 prolonged cold-stored platelets in circulation. Pretreatment of platelets with EGTA, a cell impermeable calcium ion chelator, reversely inhibited cold storage-induced platelet activation and consequently prolonged circulation of cold-stored platelets. Moreover, transfusion of EGTA-treated, cold-stored platelets, but not room temperature-stored platelets, into the mice deficient in glycoprotein Ibα significantly shortened tail-bleeding times and diminished blood loss. Conclusions: Integrin activation and apoptosis is the underlying mechanism of rapid clearance of platelets after cold storage. Addition of a cell impermeable calcium ion chelator to platelet products is potentially a simple and effective method to enable cold storage of platelets for transfusion.


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

2013 ◽  
Vol 34 (suppl 1) ◽  
pp. P4873-P4873 ◽  
Author(s):  
S. O'Connor ◽  
M. Rejane ◽  
J. Amour ◽  
J. Abtan ◽  
M. Kerneis ◽  
...  

Transfusion ◽  
2020 ◽  
Author(s):  
Melissa K. Mattson ◽  
Cory Groves ◽  
Mark M. Smith ◽  
Jon M. Christensen ◽  
Dong Chen ◽  
...  

2013 ◽  
Vol 40 (1) ◽  
pp. 22-26 ◽  
Author(s):  
Alhossain A. Khalafallah ◽  
Abdul Majeed Al-Barzan ◽  
Annette Camino ◽  
Iain K. Robertson ◽  
Gerald Bates ◽  
...  

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