scholarly journals Rare missense variants in Tropomyosin‐4 ( TPM4 ) are associated with platelet dysfunction, cytoskeletal defects and excessive bleeding

Author(s):  
Rachel J Stapley ◽  
Natalie S Poulter ◽  
Abdullah O Khan ◽  
Christopher W Smith ◽  
Patricia Bignell ◽  
...  
Blood ◽  
1990 ◽  
Vol 76 (9) ◽  
pp. 1680-1697 ◽  
Author(s):  
RC Woodman ◽  
LA Harker

Bleeding after CPB has been difficult to characterize and its treatment equally difficult to standardize. The complexity of this problem is related to the hemostatic process, the technical variations in the operative procedures, and the many uncontrolled variables associated with CPB, including the effects of anesthetic or pharmacologic agents, the nature of the priming solution, hemodilution, hypothermia, the type of oxygenator, and the use of transfused blood products. Although there are multiple and generally predictable complex changes in the hemostatic mechanism during CPB, the temporary loss of platelet function is the most common and clinically relevant. This transient platelet dysfunction occurs in all patients undergoing CPB; however, it only causes excessive bleeding in a small percentage of patients. Unfortunately, it has not yet been possible to predict which patients will develop hemorrhagic complications, although prolonged pump times are a contributing risk factor. Over the past decade there has been extensive investigation into the management of bleeding associated with CPB, provoked primarily by the increased awareness of transfusion- transmitted viral diseases and the inappropriately excessive use of homologous blood products. Several approaches to autotransfusion of shed blood and autologus blood donation have been developed to minimize perioperative homologous blood transfusion. Pharmacologic agents such as desmopressin, aprotinin, and topical fibrin glues have also been introduced to improve hemostasis during CPB. The protease inhibitor aprotinin is particularly promising in the reduction of bleeding associated with CPB when given prophylactically. Aprotinin may provide new insights into the mechanism of CPB-induced platelet dysfunction. Desmopressin is indicated only for the treatment of bleeding after CPB. The management of bleeding associated with CPB will undoubtedly


2000 ◽  
Vol 84 (11) ◽  
pp. 794-799 ◽  
Author(s):  
Annick Fiemeyer ◽  
Gilles Chatellier ◽  
Carine Chammas ◽  
Jean-François Baron ◽  
Martine Aiach ◽  
...  

SummaryPlatelet dysfunction can be a major factor in excessive bleeding following cardiopulmonary bypass (CBP). A rapid, specific and sensitive method to identify platelet dysfunction would be a useful tool for identifying patients at an increased risk of bleeding. The ability of PFA100™, an in vitro bleeding test, to predict increased bleeding risk linked to platelet dysfunction was tested in 146 patients undergoing primary coronary artery bypass graft. Blood samples were taken the day before surgery, and 15 min and 5 h after heparin neutralization. The preoperative closure times (CT), i. e. the time required for platelets in citrated whole blood to occlude an aperture cut into a membrane coated with collagen plus either epinephrine (CTEPI) or adenosine diphosphate (CTADP) were longer in blood-group-O patients than in patients with other groups. The 15 min postoperative values were significantly longer from preoperative values essentially owing to CBP-induced hemodilution. Interestingly, 5 h after CBP, a significant reduction in CT values probably reflected platelet hyperaggregability. No correlation was found between calculated blood loss (CBL) and either preoperative or postoperative PFA values.


2019 ◽  
Vol 03 (01) ◽  
pp. 24-27
Author(s):  
Sandeep Sharan ◽  
Ajay Gandhi ◽  
Poonam Malhotra Kapoor

AbstractPatients undergoing cardiac surgery are at risk of excessive bleeding and associated complications. Excessive bleeding during and after cardiac surgery has an incidence of ~20%. Massive bleeding and subsequent requirement for blood product administration and mediastinal re-exploration is associated with significant morbidity and mortality. Postoperative, nonsurgical bleeding in cardiac surgical patients is often multifactorial. Platelet dysfunction, excessive fibrinolysis, hypothermia, preoperative anemia, and deficiency of coagulation factors or their dilution are all suggested etiologies of postoperative bleeding. Among these, the most important is thought to be platelet dysfunction, which occurs as a result of the interplay of acquired and pharmacologically induced factors. Patients suffering from coronary artery disease are usually advised to stop antiplatelet medication a few days prior to coronary artery bypass grafting (CABG) to reduce the incidence of postoperative bleeding. However, patients who are still on antiplatelet drugs are at an increased risk of postoperative bleeding. Currently, the transfusion of blood and blood components to manage postoperative bleeding after CABG remains largely empirical, with considerable variation among institutions. Algorithm-based hemostatic therapy has been shown to be superior to empiric hemostatic therapy that is based on clinical judgment. Hence, there is a need to have objective tests to demonstrate platelet dysfunction before platelet transfusion. Several devices of platelet function tests have been reported in clinical studies to evaluate platelet dysfunction and quantify the need for antiplatelet therapy


Author(s):  
Ryan Bayusantika Ristandi ◽  
Nida Suraya ◽  
Leni Lismayanti ◽  
Sylvia Rachmayati

Postoperative heart patients with Cardiopulmonary Bypass (CPB) are at risk of excessive bleeding. Excessive bleeding is mainly due to thrombocytopenia and platelet dysfunction. The volume of post-CPB bleeding without the administration of platelet concentrate correlates well with platelet count and Maximum Amplitude (MA). The administration of platelet concentrate in thrombocytopenia and platelet dysfunction post CPB may affect the correlation of platelet count and MA which affects the volume of bleeding. The purpose of this research was to know the role of transfusion of platelet concentration post-CPB on the correlation between platelet number and MA with the volume of bleeding. The analytical observational analytic test with the cross-sectional design was conducted on secondary data from September 2015 to March 2016. A total of 44 postoperative heart patients CPB monitored up to four hours in the room Cardiac Intensive Care Unit (CICU) Dr. HasanxSadikin HospitalxBandung. The platelet count was negatively correlated with bleeding volume (r = -0.157, p = 0.308) and the MA was negatively correlated (very weak) with bleeding volume (r = -0.171, p = 0.266). The post-CPB platelet concentrate concentration led to better patient hemostasis, as evidenced by the majority of platelet counts (97.7%)> 100,000/mm3 and MA (84%)x≥x50xmm. The post-CPB platelet concentrate causes a negative (very weak) correlation between platelet count and MA with bleeding volume


Blood ◽  
1990 ◽  
Vol 76 (9) ◽  
pp. 1680-1697 ◽  
Author(s):  
RC Woodman ◽  
LA Harker

Abstract Bleeding after CPB has been difficult to characterize and its treatment equally difficult to standardize. The complexity of this problem is related to the hemostatic process, the technical variations in the operative procedures, and the many uncontrolled variables associated with CPB, including the effects of anesthetic or pharmacologic agents, the nature of the priming solution, hemodilution, hypothermia, the type of oxygenator, and the use of transfused blood products. Although there are multiple and generally predictable complex changes in the hemostatic mechanism during CPB, the temporary loss of platelet function is the most common and clinically relevant. This transient platelet dysfunction occurs in all patients undergoing CPB; however, it only causes excessive bleeding in a small percentage of patients. Unfortunately, it has not yet been possible to predict which patients will develop hemorrhagic complications, although prolonged pump times are a contributing risk factor. Over the past decade there has been extensive investigation into the management of bleeding associated with CPB, provoked primarily by the increased awareness of transfusion- transmitted viral diseases and the inappropriately excessive use of homologous blood products. Several approaches to autotransfusion of shed blood and autologus blood donation have been developed to minimize perioperative homologous blood transfusion. Pharmacologic agents such as desmopressin, aprotinin, and topical fibrin glues have also been introduced to improve hemostasis during CPB. The protease inhibitor aprotinin is particularly promising in the reduction of bleeding associated with CPB when given prophylactically. Aprotinin may provide new insights into the mechanism of CPB-induced platelet dysfunction. Desmopressin is indicated only for the treatment of bleeding after CPB. The management of bleeding associated with CPB will undoubtedly


1995 ◽  
Vol 21 (S 02) ◽  
pp. 66-70 ◽  
Author(s):  
Noriyuki Tabuchi ◽  
Izaak Tigchelaar ◽  
Willem Van Oeveren

The contribution of platelet dysfunction to the impaired hemostasis after cardiac surgery remains to be established, because there is no sensitive method to assess platelet function. Measurement of the shear-induced pathway of platelet function, an important mechanism in inducing hemostasis, became possible by a novel shear-inducing technique, the in-vitro bleeding test (Thrombostat 4000). By using this test, the changes in platelet function during cardiopulmonary bypass and their contribution to hemostasis were investigated in patients undergoing cardiac surgery. Platelet function is quickly impaired shortly after the start of cardiopulmonary bypass, and partly recovered at the end of cardiopulmonary bypass. The function of aspirin-treated platelets is more severely affected than of nonaspirin platelets during cardiopulmonary bypass. Furthermore, the degree of platelet dysfunction at the end of the operation, but neither the platelet number nor the activated clotting time, was significantly correlated with blood loss from the chest drain after cardiac surgery. These results indicate the significant and variable effects of cardiopulmonary bypass on the shear-induced pathway of platelet function. Moreover, the impairment of this function of platelets appears to be a major cause of excessive bleeding in patients after cardiac surgery. Therefore, the routine use of the shear-inducing test seems helpful to make a proper diagnosis and design the therapy for bleeders after cardiac surgery.


1991 ◽  
Vol 65 (04) ◽  
pp. 355-359 ◽  
Author(s):  
E Gray ◽  
J Watton ◽  
S Cesmeli ◽  
T W Barrowcliffe ◽  
D P Thomas

SummaryThe in vitro anticoagulant activities of recombinant desulphatohirudin (r-hirudin) were studied in the activated partial thromboplastin time (APTT) and the thrombin generation test : systems. In the APTT at concentrations below 5 μg/ml, r-hirudin showed a dose-response curye. At concentrations above 5 μg/ml, the plasma became unclottable, but in the thrombin generation test , at least 10 μg/ml of r-hirudin was required for full inhibition of thrombin generation. The antithrombotic effect was assessed using a rabbit venous stasis model; 150 μg/ml r-hirudin completely prevented thrombus formation at 10 and 20 min stasis. At antithrombotic dose, the mean bleeding time ratio measured in a rabbit ear template model, was not prolonged over control values. At higher doses, the bleeding time ratios were higher than those observed for the same dosage of heparin. These data indicate that while r-hirudin is an effective antithrombotic agent, antithrombotic doses have to be carefully titrated to avoid excessive bleeding.


1976 ◽  
Vol 36 (01) ◽  
pp. 200-207 ◽  
Author(s):  
Donald G. Corby ◽  
Thomas F. Zuck

SummaryPer cent aggregation, release and content of adenine nucleotides, and specific radioactivity were evaluated in citrated platelet-rich plasma (PRP) prepared from paired samples of maternal and cord blood. Platelets of newborn infants aggregated normally in response to high dose ADP (20 μM), strong collagen suspensions, and thrombin; however, when compared with PRP from the mothers or from normal adults, per cent aggregation in response to lower concentrations of ADP (2 μM), weak collagen, and part particularly epinephrine was markedly reduced. Nucleotide release after stimulation of the newborns’ PRP with the latter two inducers was also impaired. ATP and ADP content of the newborns’ platelets was also significantly less than that of their mothers or of normal adults, but specific activity was normal. The data suggest that the impairment of ADP release in the platelets of newborn infants is due to decreased sensitivity to external stimuli. Since metabolic ATP is necessary for the platelet release reaction, it is postulated that the platelet dysfunction results from a lack of metabolic ATP.


1978 ◽  
Vol 40 (02) ◽  
pp. 532-541 ◽  
Author(s):  
Anders Lagrelius ◽  
Nils-Olov Lunell ◽  
Margareta Blombäck

SummaryThe aim of the present study was to investigate the effect on blood coagulation and fibrinolysis of a natural oestrogen preparation, piperazine oestrone sulphate, prospectively in menopausal women. Scopolamine was given to the control group.The women were investigated before and during treatment with regard to factors VIII, VII, X, V, fibrinopeptide A, antithrombin III, plasminogen, rapid antiplasmin and α1-antitrypsin. There was no significant change towards hypercoagulability or decreased fibrinolysis in any group. In the oestrogen group, however, a tendency towards an increased level of plasminogen and a decreased level of antiplasmin was demonstrated. In the scopolamine group there was an unexpected fall in factors X and V and also in plasminogen and α1,-antitrypsin. A low level of some blood coagulation factors in some of the women before treatment is somewhat astonishing; none of them had any history of excessive bleeding.


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