Hollace MacGregor

Heparin causes platelet dysfunction and induces fibrinolysis before cardiopulmonary bypass

BACKGROUND Platelet dysfunction and increased fibrinolysis are the most important etiologic factors in the hemostatic defect observed following the institution of cardiopulmonary bypass. This study examined the effects of heparin per se, administered before the institution of cardiopulmonary bypass, on platelet function and fibrinolysis. METHODS Sampling was performed in 55 patients undergoing cardiac operations before and 5 minutes after the routine administration of heparin, before the institution of cardiopulmonary bypass. RESULTS Heparin administration resulted in a significant prolongation of the bleeding time (from 6.3 +/- 2.1 to 12.6 +/- 4.9 minutes; p < 0.00001), a significant reduction in the level of shed blood thromboxane B2 (from 1,152 +/- 669 to 538 +/- 187 pg/0.1 mL; p = 0.00002), and an increase in the plasma levels of plasmin (from 11.8 +/- 9.7 to 125.4 +/- 34.8 U/L; p < 0.0001) and D-dimer (from 571.3 +/- 297.1 to 698.5 +/- 358.6 micrograms/mL; p = 0.05). There were no significant differences before and after heparin administration in the plasma levels of fibrinogen, plasminogen, tissue plasminogen activator, antiplasmin, antithrombin III, and von Willebrand factor. CONCLUSIONS Heparin, independent of cardiopulmonary bypass, causes both platelet dysfunction and increased fibrinolysis. The use of an alternative anticoagulant or a lower dose of heparin in conjunction with heparin-coated surfaces might improve the hemostatic balance during open heart operations.

Comparison of the effects of transfusions of cryopreserved and liquid-preserved platelets on hemostasis and blood loss after cardiopulmonary bypass

OBJECTIVE The aim of the study was to compare the clinical effects and hemostatic efficiency of transfusions of platelets preserved in the frozen state for as long as 2 years with transfusions of platelets preserved in the conventional manner for as long as 5 days in patients undergoing cardiopulmonary bypass. METHODS Seventy-three patients were prospectively randomly assigned to receive transfusions of cryopreserved or liquid-preserved platelets. Nonsurgical blood loss was measured during and after the operation. Bleeding time, hematologic variables, and the bleeding time site shed blood were assayed before cardiopulmonary bypass and at 30 minutes and 2, 4, and 24 hours after transfusion. In vitro platelet function tests were conducted on platelets obtained from healthy volunteers. RESULTS No adverse sequelae of the transfusions were observed. Blood loss and the need for postoperative blood product transfusions were lower in the group receiving cryopreserved platelets. Lower posttransfusion platelet increments and a tendency toward decreased platelet survival were observed in patients receiving cryopreserved platelets. Hematocrit and plasma fibrinogen were significantly higher in this group, and the duration of intubation was shorter. In vitro, cryopreserved platelets demonstrated less aggregation, lower pH, and decreased response to hypotonic stress but generated more procoagulant activity and thromboxane. CONCLUSIONS (1) Cryopreserved platelet transfusions are superior to liquid-preserved platelets in reducing blood loss and the need for blood product transfusions after cardiopulmonary bypass. (2) The reduction in blood loss in the patients receiving cryopreserved platelet transfusions after cardiopulmonary bypass probably reflects improved in vivo hemostatic function of cryopreserved platelets. (3) Some in vitro measures of platelet quality (aggregation, pH, hypotonic stress) may not reflect in vivo quality of platelet transfusions after cardiopulmonary bypass, whereas other in vitro measures (platelet procoagulant activity and thromboxane) do.

Fresh, liquid-preserved, and cryopreserved platelets: adhesive surface receptors and membrane procoagulant activity

BACKGROUND: A study in humans showed that the transfusion of previously frozen human platelets after cardiopulmonary bypass, despite decreased survival, resulted in better hemostatic function than that of liquid‐preserved platelets stored at 22°C for 3 to 4 days.

Limitations of the hematocrit level to assess the need for red blood cell transfusion in hypovolemic anemic patients

BACKGROUND:  The transfusion trigger that physicians use to determine whether a patient requires a red blood cell (RBC) transfusion is the peripheral venous hematocrit (Hct) value. Although this measurement is an indicator of the concentration of RBCs in the blood, it does not reveal the RBC volume, plasma volume, or total blood volume, nor does it give any indication of whether the patient is hypovolemic, normovolemic, or hypervolemic.

The effects of aspirin and hypothermia on platelet function in vivo

Patients undergoing hypothermic cardiopulmonary bypass are often receiving aspirin therapy. Hypothermia, aspirin and cardiopulmonary bypass can each induce a platelet function defect, but it is not known if the effects of aspirin and hypothermia are additive in this regard. To address this question in humans in vivo, the forearm skin temperature of healthy volunteers was equilibrated and maintained at either normothermia (32°C) or hypothermia (28°C or 22°C) before and 16 h after the ingestion of 650 mg aspirin. A standardized template bleeding time was performed on the forearm and the shed blood emerging from the wound was assayed for platelet surface P‐selectin expression by whole blood flow cytometry (reflecting α granule secretion) and thromboxane B2 (the stable metabolite of thromboxane A2) by radioimmunoassay. Hypothermia resulted in marked prolongation of the bleeding time. Aspirin resulted in prolongation of the bleeding time under normothermic conditions, but only minimally augmented the hypothermia‐induced prolongation of the bleeding time. Platelet surface P‐selectin up‐regulation in shed blood was abolished by hypothermia. Aspirin had no effect on maximal platelet surface P‐selectin expression under normothermic or hypothermic conditions. Both hypothermia and aspirin resulted in markedly reduced shed blood thromboxane B2. Although aspirin slightly augmented the hypothermia‐induced reduction in shed blood thromboxane B2, the concentration of thromboxane generated in shed blood under hypothermic conditions in the absence of aspirin had no effect on platelet surface P‐selectin or platelet aggregation in whole blood. In conclusion, as determined by three independent parameters of the shed blood emerging from a standardized bleeding time wound (bleeding time, platelet surface P‐selectin, and thromboxane B2), aspirin did not significantly augment hypothermia‐induced platelet dysfunction in vivo.

Correlation between in vitro aggregation and thromboxane A2 production in fresh, liquid-preserved, and cryopreserved human platelets: effect of agonists, pH, and plasma and saline resuspension.

BACKGROUND: Some of the tests used to assess the quality of fresh and preserved platelets (PLTs) include PLT number, PLT morphology, pH of the PLT medium, PLT response to hypotonic stress, and PLT aggregation to agonists. This study was performed to assess the function of fresh and preserved PLTs by their response to aggregation and their production of thromboxane A2 after in vitro stimulation with agonists.

Circulation and hemostatic function of autologous fresh, liquid‐preserved, and cryopreserved baboon platelets transfused to correct an aspirin‐induced thrombocytopathy

BACKGROUND : The survival of fresh and preserved platelets has been used primarily to determine their therapeutic effectiveness. The function of the fresh and preserved platelets has been difficult to assess. In stable thrombocytopenic patients, platelet function of fresh and preserved allogeneic platelets is evaluated by the reduction in bleeding time. In this study of healthy male baboons, both the survival and function of autologous fresh, liquid‐preserved, and cryopreserved platelets in the correction of an aspirin‐induced thrombocytopathy was evaluated.

Circulation and distribution of autotransfused fresh, liquid‐preserved and cryopreserved baboon platelets

Background and Objectives Studies were carried out in five healthy male baboons to determine the 111indium oxine (111In‐oxine) survival of autologous fresh, liquid‐preserved and cryopreserved platelets. Simultaneous organ‐distribution studies were performed to determine the percentage uptake of platelets by the spleen and/or liver.

Survival of baboon biotin-X-N-hydroxysuccinimide and 111In-oxine-labelled autologous fresh and lyophilized reconstituted platelets

Background and Objectives  In accordance with Food and Drug Administration (FDA) regulations, platelets can be stored in the liquid state at 22 °C for only 5 days. Platelets frozen with 6% dimethylsulphoxide (DMSO) can be stored at −80 °C for 2 years, and platelets frozen with 5% DMSO can be stored at −150 °C for 3 years. Studies are being conducted to determine the effects of lyophilization of platelets. In the present study, we assessed the survival of autologous lyophilized‐reconstituted platelets in the baboon.

Platelet surface p‐selectin, platelet–granulocyte heterotypic aggregates, and plasma‐soluble p‐selectin during plateletpheresis

BACKGROUND: Plateletpheresis components have been shown to contain p‐selectin‐positive platelets after collection and storage. P‐selectin mediates binding of activated platelets to granulocytes and monocytes. This study was undertaken to assess platelet activation, granulocyte activation, platelet–granulocyte heterotypic aggregate formation, and the plasma‐soluble p‐selectin level during plateletpheresis performed on a particular instrument (MCS+, Haemonetics).