Utility of whole blood hemostatometry using the clot signature analyzer for assessment of hemostasis in cardiac surgery

BACKGROUND: A hemostatic monitor capable of rapid, accurate detection of clinical coagulopathy within the operating room could improve management of bleeding after cardiopulmonary bypass (CPB). The Clot Signature Analyzer is a hemostatometer that measures global hemostasis in whole blood. The authors hypothesized that point-of-care hemostatometry could detect a clinical coagulopathic state in cardiac surgical patients. METHODS: Fifty-seven adult patients scheduled for a variety of elective cardiac surgical procedures were studied. Anesthesia, CPB, heparin anticoagulation, protamine reversal, and transfusion for post-CPB bleeding were all managed by standardized protocol. Clinical coagulopathy was defined by the need for platelet or fresh frozen plasma transfusion. The Clot Signature Analyzer collagen-induced thrombus formation (CITF) assay measured platelet-mediated hemostasis in vitro. The activated clotting time, platelet count, prothrombin time, activated partial thromboplastin time, and fibrinogen concentration were also measured. RESULTS: The postprotamine CITF was greater in patients who required hemostatic transfusion than in those who did not (17.6 +/- 8.0 min vs. 10.5 +/- 5.7 min, respectively; P < 0.01). Postprotamine CITF values were highly correlated with platelet and fresh frozen plasma transfusion (Spearman r = 0.50, P < 0.001 and r = 0.40, P < 0.005, respectively). Receiver operator characteristic curves showed a highly significant relation between the postprotamine CITF and intraoperative platelet and fresh frozen plasma transfusion (area under the curve, 0.78-0.81, P < 0.005) with 60-80% sensitivity, specificity, positive and negative predictive values at cutoffs of 12-14 min. Logistic regression demonstrated that the CITF was independently predictive of post-CPB hemostatic transfusion, but standard hemostatic assays were not. CONCLUSIONS: The Clot Signature Analyzer CITF detects a clinical coagulopathic state after CPB and is independently predictive of the need for hemostatic transfusion. Hemostatometry has potential utility for monitoring hemostasis in cardiac surgery.     

Allogenic blood transfusion for surgery

Blood transfusion against surgical patients is mainly as a replacement therapy for intra-operative bleeding. Transfusion trigger depends on to maintain 12 ml/kg/min oxygen carrying capacity. Oxygen consumption depends on oxygen carrying capacity which multiplicity hemoglobin concentration and cardiac output. The government of United States decided the transfusion trigger of surgical patients at hemoglobin 7.0 g/dl except patients who have cardiac problem at 1988. The indication of plasma and platelet transfusion is limited in surgical field. Because bleeding tendency is usually a contra-indication of surgery itself. Dilution coagulopathy due to massive bleeding exceed one blood volume is the main indication of plasma and platelet transfusion. It is necessary to administrate fresh frozen plasma for replenishing coagulation function with 30% of one body plasma volume when prothrombin time prolong more than 16 seconds. Platelet transfusion is effective for hemostasis in case of massive bleeding which exceed 1.5 blood volume and also peripheral blood platelet count indicate lower than 50,000/mm3.     

Optimization of thromboelastography-guided platelet transfusion in cardiovascular surgery

Objectives  

Platelet dysfunction is a major cause of bleeding complications in patients undergoing cardiovascular surgery under cardiopulmonary bypass (CPB). Thromboelastography (TEG) can be used to assess post-CPB coagulopathy, but its utility in guiding platelet transfusion (PT) after CPB is unclear. This study assessed the utility of a TEG-guided PT protocol in patients undergoing cardiovascular surgery under CPB.     

Efficacy of a Simple Intraoperative Transfusion Algorithm for Nonerythrocyte Component Utilization after Cardiopulmonary Bypass

Background: Abnormal bleeding after cardiopulmonary bypass (CPB) is a common complication of cardiac surgery, with important health and economic consequences. Coagulation test-based algorithms may reduce transfusion of non-erythrocyte allogeneic blood in patients with abnormal bleeding.

Methods: The authors performed a randomized prospective trial comparing allogeneic transfusion practices in 92 adult patients with abnormal bleeding after CPB. Patients with abnormal bleeding were randomized to one of two groups: a control group following individual anesthesiologist's transfusion practices and a protocol group using a transfusion algorithm guided by coagulation tests.

Results: Among 836 eligible patients having all types of elective cardiac surgery requiring CPB, 92 patients developed abnormal bleeding after CPB (incidence, 11%). The transfusion algorithm group received less allogeneic fresh frozen plasma in the operating room after CPB (median, 0 units; range, 0-7 units) than the control group (median, 3 units; range, 0-10 units) (P = 0.0002). The median number of platelet units transfused in the operating room after CPB was 4 (range, 0-12) in the algorithm group compared with 6 (range, 0-18) in the control group (P = 0.0001). Intensive care unit (ICU) mediastinal blood loss was significantly less in the algorithm group. Multivariate analysis demonstrated that transfusion algorithm use resulted in reduced ICU blood loss. The control group also had a significantly greater incidence of surgical reoperation of the mediastinum for bleeding (11.8%vs. 0%;P = 0.032).     

Use of recombinant factor VIIa for uncontrolled bleeding in neonates after cardiopulmonary bypass

Background:  Increasingly, recombinant activated factor VII (rFVIIa) is used adjunctively in nonhemophiliacs to control hemorrhage unresponsive to conventional therapy in a variety of settings including postcardiopulmonary bypass (CPB). Studies examining rFVIIa administration to neonates after CPB are limited. The goal of this study was to evaluate retrospectively the clinical outcomes of neonates treated at our institution with rFVIIa for uncontrolled post-CPB bleeding.
Methods:  We retrospectively identified eight neonates undergoing complex congenital cardiac surgery who received rFVIIa, either intraoperatively or postoperatively, for uncontrolled post-CPB bleeding. Transfusion trends and prothrombin times (PT) were assessed both pre- and post-rFVIIa administration. Chest tube drainage volumes were recorded pre- and post-rFVIIa administration in those neonates receiving rFVIIa postoperatively in the intensive care unit. We documented such adverse events as thrombosis, dialysis (hemodialysis and peritoneal dialysis), extracorporeal membrane oxygenation (ECMO) and in-hospital mortality.
Results:  The mean amount of transfused packed red blood cells, platelets and fresh frozen plasma decreased significantly after the administration of rFVIIa. Transfusion of cryoprecipitate trended towards a decrease but did not reach statistical significance. PT values also decreased significantly after the administration of rFVIIa. A high mortality was found in neonates exposed to both rFVIIa and ECMO; however, this was not significantly different from the mortality of neonates exposed to ECMO alone.
Conclusions:  Administration of rFVIIa to neonates for the treatment of uncontrolled post-CPB bleeding significantly reduced transfusion requirements and normalized PT values. Future randomized, controlled trials are needed to evaluate the potential hemostatic benefit and adverse effects of rFVIIa administration to neonates following CPB.     

Platelet-rich plasma sequestration, with therapeutic platelet yields, reduces allogeneic transfusion in complex cardiac surgery

Platelet dysfunction is the most common cause of nonsurgical bleeding after cardiopulmonary bypass (CPB). We hypothesized that reinfusion of a therapeutic quantity of platelets sequestered before CPB would decrease the need for allogeneic platelet transfusion, as well as decrease bleeding and total allogeneic transfusion, in cardiac surgery patients at moderately high risk for bleeding. Fifty-five patients undergoing either reoperative coronary artery bypass (CABG) or combined CABG and valve replacement were randomized to control or platelet-rich plasma sequestration (pheresis) groups. All patients received intraoperative epsilon-aminocaproic acid infusions. There was no significant difference between groups with respect to preoperative characteristics, duration of CPB, or target postoperative hematocrit. Mean platelet yields were 6.2 +/- 2.1 units (3.1 x 10(11) platelets). Mean pheresis time was 44 min. Allogeneic platelets (range = 6-12 units) were transfused to 28% of control patients, compared with 0% of pheresis patients (P < 0.01). Allogeneic packed red blood cells were transfused to 45% of control patients (1.2 units per patient) versus 31% of pheresis patients (0. 7 unit per patient) (P = 0.35). Total allogeneic units transfused were significantly reduced in the pheresis group (P < 0.02). Mediastinal chest tube drainage was not significantly decreased in the pheresis group. In this prospective, randomized study, therapeutic platelet yields were obtained before CPB. In contrast with recent studies with low platelet yields, these data support the conclusion that platelet-rich plasma sequestration is effective in reducing allogeneic platelet transfusions and total allogeneic units transfused in cardiac surgery patients at moderately high risk for post-CPB coagulopathy and bleeding. IMPLICATIONS: Transfusion of allogeneic blood products, including platelets, is common during complex cardiac surgical procedures. In the present prospective, randomized study, a significant reduction in allogeneic platelet transfusion and total allogeneic units transfused was observed after the reinfusion of a therapeutic quantity of autologous platelets sequestered before cardiopulmonary bypass.     

Massive transfusion and coagulopathy: pathophysiology and implications for clinical management

PURPOSE: To review the pathophysiology of coagulopathy in massively transfused, adult and previously hemostatically competent patients in both elective surgical and trauma settings, and to recommend the most appropriate treatment strategies. METHODS: Medline was searched for articles on "massive transfusion," "transfusion," "trauma," "surgery," "coagulopathy" and "hemostatic defects." A group of experts reviewed the findings. Principal findings: Coagulopathy will result from hemodilution, hypothermia, the use of fractionated blood products and disseminated intravascular coagulation. The clinical significance of the effects of hydroxyethyl starch solutions on hemostasis remains unclear. Maintaining a normal body temperature is a first-line, effective strategy to improve hemostasis during massive transfusion. Red cells play an important role in coagulation and hematocrits higher than 30% may be required to sustain hemostasis. In elective surgery patients, a decrease in fibrinogen concentration is observed initially while thrombocytopenia is a late occurrence. In trauma patients, tissue trauma, shock, tissue anoxia and hypothermia contribute to the development of disseminated intravascular coagulation and microvascular bleeding. The use of platelets and/or fresh frozen plasma should depend on clinical judgment as well as the results of coagulation testing and should be used mainly to treat a clinical coagulopathy. CONCLUSIONS: Coagulopathy associated with massive transfusion remains an important clinical problem. It is an intricate, multifactorial and multicellular event. Treatment strategies include the maintenance of adequate tissue perfusion, the correction of hypothermia and anemia, and the use of hemostatic blood products to correct microvascular bleeding.     

Efficacy of a simple intraoperative transfusion algorithm for nonerythrocyte component utilization after cardiopulmonary bypass

BACKGROUND: Abnormal bleeding after cardiopulmonary bypass (CPB) is a common complication of cardiac surgery, with important health and economic consequences. Coagulation test-based algorithms may reduce transfusion of non-erythrocyte allogeneic blood in patients with abnormal bleeding. METHODS: The authors performed a randomized prospective trial comparing allogeneic transfusion practices in 92 adult patients with abnormal bleeding after CPB. Patients with abnormal bleeding were randomized to one of two groups: a control group following individual anesthesiologist's transfusion practices and a protocol group using a transfusion algorithm guided by coagulation tests. RESULTS: Among 836 eligible patients having all types of elective cardiac surgery requiring CPB, 92 patients developed abnormal bleeding after CPB (incidence, 11%). The transfusion algorithm group received less allogeneic fresh frozen plasma in the operating room after CPB (median, 0 units; range, 0-7 units) than the control group (median, 3 units; range, 0-10 units) (P = 0.0002). The median number of platelet units transfused in the operating room after CPB was 4 (range, 0-12) in the algorithm group compared with 6 (range, 0-18) in the control group (P = 0.0001). Intensive care unit (ICU) mediastinal blood loss was significantly less in the algorithm group. Multivariate analysis demonstrated that transfusion algorithm use resulted in reduced ICU blood loss. The control group also had a significantly greater incidence of surgical reoperation of the mediastinum for bleeding (11.8% vs. 0%; P = 0.032). CONCLUSIONS: Use of a coagulation test-based transfusion algorithm in cardiac surgery patients with abnormal bleeding after CPB reduced non-erythrocyte allogeneic transfusions in the operating room and ICU blood loss.     

Thrombography reveals thrombin generation potential continues to deteriorate following cardiopulmonary bypass surgery despite adequate hemostasis

The intrinsic and extrinsic activation pathways of the hemostatic system converge when prothrombin is converted to thrombin. The ability to generate an adequate thrombin burst is the most central aspect of the coagulation cascade. The thrombin-generating potential in patients following cardiopulmonary bypass (CPB) may be indicative of their hemostatic status. In this report, thrombography, a unique technique for directly measuring the potential of patients' blood samples to generate adequate thrombin bursts, is used to characterize the coagulopathic profile in post-CPB patients. Post-CPB hemostasis is typically achieved with protamine reversal of heparin anticoagulation and occasionally supplemented with blood product component transfusions. In this pilot study, platelet poor plasma samples were derived from 11 primary cardiac surgery patients at five time points: prior to CPB, immediately post-protamine, upon arrival to the intensive care unit (ICU), 3 hours post-ICU admission, and 24 hours after ICU arrival. Thrombography revealed that the Endogenous Thrombin Potential (ETP) was not different between [Baseline] and [PostProtamine] but proceeded to deteriorate in the immediate postoperative period. At the [3HourPostICU] time point, the ETP was significantly lower than the [Baseline] values, 1233 +/- 591 versus 595 +/- 379 nM.min (mean +/- SD; n=9, p < .005), despite continued adequacy of hemostasis. ETPs returned to baseline values the day after surgery. Transfusions received, conventional blood coagulation testing results, and blood loss volumes are also presented. Despite adequate hemostasis, thrombography reveals an underlying coagulopathic process that could put some cardiac surgical patients at risk for postoperative bleeding. Thrombography is a novel technique that could be developed into a useful tool for perfusionists and physicians to identify coagulopathies and optimize blood management following CPB.     

Coagulation Profile of Neonates Undergoing Arterial Switch Surgery With Crystalloid Priming of the Cardiopulmonary Bypass Circuit

ObjectivesThe aim was to evaluate changes in the coagulation profile of cyanotic neonates, to analyze the effects of cardiopulmonary bypass (CPB) with crystalloid priming on their coagulation status, and to determine factors predicting a requirement for hemostasis-derived transfusion.DesignRetrospective cohort.SettingSingle-center, tertiary academic hospital.ParticipantsIn total, 100 consecutive neonates who underwent arterial switch surgery between December 2014 and June 2020.InterventionsRotational thromboelastometry (ROTEM) and coagulation parameters before surgery and before termination of CPB were evaluated. Transfusion of platelets, fresh frozen plasma, and fibrinogen, defined as hemostasis-derived transfusion (HD transfusion), were determined. Patients with and without HD transfusion were compared to identify predictors.Measurements and Main ResultsAfter CPB, fibrinogen was reduced by 24.5% (interquartile range [IQR] 8.9-32.1) to 201 mg/dL (IQR 172-249), resulting in a reduction of FIBTEM A10 by 20% (1.8-33.3) to 8 mm (6-11). The platelet count decreased by a median of 47.2% (25.6-61.3) to 162 × 10³/µL (119-215). However, the median fibrinogen concentration and platelet count remained within normal range. Neonates with abnormal ROTEM results were more likely to receive HD transfusions. The HD transfusions were more likely with lower preoperative FIBTEM maximum clot firmness values (p = 0.031), lower hemoglobin concentrations at termination of CPB (p = 0.02), and longer CPB duration (p = 0.017). Perioperative hemostasis without any HD transfusion was achieved in 64 neonates.ConclusionsGuidance from ROTEM analyses facilitates hemostasis management after neonatal CPB. Circuit miniaturization with transfusion-free CPB is associated with acceptable changes in ROTEM in most patients, and allows sufficient hemostasis without any HD transfusions in most patients.     

Gerinnungsmanagement bei Eingriffen mit extrakorporaler Zirkulation

After cardiac surgery with extracorporeal circulation, approximately 20% of patients show significant bleeding tendencies and 5% require re-intervention. In 50% of patients undergoing re-operation, no surgical cause can be determined, suggesting coagulopathy after cardiopulmonary bypass (CPB). For perioperative management of transfusion of blood products and coagulation factor concentrates, a clinical algorithm for the perioperative hemostatic therapy in patients undergoing cardiac surgery with CPB has been developed. The currently available evidence and the point of care methods routinely accessible in our institution (blood gas analysis, ACT, point of care Quick value, aPTT and platelet count) were used. The intervention with plasma products, coagulation factor concentrates and hemostatic drugs after extracorporeal circulation are described. Extensive bleeding history as well as the efficacy and side effects of antifibrinolytic treatment are discussed.     

The effects of heparin, protamine, and heparin/protamine reversal on platelet function under conditions of arterial shear stress.

Platelet dysfunction contributes to blood loss after cardiopulmonary bypass. This study examined the antiplatelet effects of heparin, protamine, and varying heparin/protamine ratios in an in vitro physiologic model and further elucidated the mechanism of the antiplatelet and anticoagulant effects of protamine. We used the Clot Signature Analyzer (CSA(TM)), a system that analyzes coagulation in flowing whole blood, to test two aspects of platelet function, with different concentrations of heparin and protamine, under conditions simulating arterial flow: collagen-induced thrombus formation (CITF) under moderate shear and high shear platelet activation, platelet hemostasis time (PHT). In addition, platelet aggregometry, celite activated clotting time (Hepcon(TM) ACT), prothrombin time (PT), and partial thromboplastin time (PTT) were measured. Both PHT and the CITF were prolonged by heparin at 20 microg/mL, protamine at 20 and 40 microg/mL, and heparin/protamine ratios of 1:1 and 1:2, but not at 1:1.5. The Hepcon ACT was prolonged by heparin 20 microg/mL and protamine alone at 20 and 40 microg/mL, was normal at a ratio of 1:1, and was prolonged at 1:1.5 and 1:2. Protamine 80 microg/mL prolonged the PT and PTT. Dependency on thrombin, protein kinase C activation, and nonspecific charge effects were examined. The direct thrombin inhibitor D-phenylalanyl-L-prolyl-L-arginyl-chloromethyl ketone prolonged the PHT and ACT, but not the CITF, whereas the polycationic molecules polyarginine and polylysine prolonged the CITF, but not the PHT. The effect of protamine on the PTT, but not PT, could be shortened by the addition of excess phospholipid. Therefore, heparin inhibits both high shear collagen-independent and moderate shear collagen-dependent platelet activation; however, the latter is not mediated by its antithrombin activity. Protamine's antithrombin effect may explain its inhibition of platelet activation at high shear stress. Protamine's nonspecific charge effects are more important for inhibiting moderate shear collagen-induced platelet activation. Implications: This study suggests that protamine reversal of heparin's antiplatelet effect occurs within a narrow window because of the direct antiplatelet effects of protamine. Antithrombin effects may explain the inhibition of shear activation of platelets by both heparin and protamine. Nonspecific charge effects of protamine may explain the inhibition of collagen platelet activation in the presence of medium shear.     

The role of prophylactic fresh frozen plasma in decreasing blood loss and correcting coagulopathy in cardiac surgery. A systematic review

Summary Fresh frozen plasma is commonly used in cardiac surgery in an attempt to replace clotting factors and to decrease bleeding. Despite this, there has been no previous review of the available literature to support this practice. The aim of this review was to study the effect of prophylactic peri-operative transfusion of fresh frozen plasma on bleeding and coagulopathy in patients undergoing cardiac surgery. A comprehensive literature search was performed and all randomised controlled trials of the use of fresh frozen plasma in cardiac surgery were included. Six small trials were found that included a total of 363 participants with six different dose regimens of fresh frozen plasma. The overall quality of the studies was poor due to small patient numbers and lack of allocation concealment. There was no evidence that the prophylactic use of fresh frozen plasma affected peri-operative blood loss in cardiac surgery. There was some evidence that it may improve platelet count and fibrinogen concentration.     

Questionnaire survey of anesthesiologists' opinion regarding the Japanese guidelines for transfusion

BACKGROUND: Anesthesiologists' opinions regarding the Japanese guidelines for transfusion were surveyed. METHODS: From December 28, 2004 to January 28, 2005 a questionnaire survey was performed in 958 hospitals registered with the Japanese Society for Anesthesiologists. Queries regarding the guidelines for packed red cells, fresh frozen plasma, platelet concentrates, autologous blood transfusions, and other miscellaneous subjects were sent to these hospitals. RESULTS: A total of 537 hospitals (56.1%) responded to the survey. The guidelines for packed red cells were complied with and widely accepted. The trigger value of hemoglobin concentration was 7-9 g x dl(-1). Although 54.4% of the anesthesiologists used the coagulation disorder as the triggering factor for transfusion of fresh frozen plasma, only 19.6% of the hospitals monitored coagulopathy. In most hospitals, the trigger value of hemorrhage for use of fresh frozen plasma was the bleeding amount of less than 3000 ml, which is less than 70% of the recommended triggering value (bleeding exceeding 100% of circulating blood volume). The guideline for platelet concentrate transfusions for elective surgery was somewhat accepted (77.1%), but the triggering value; 3 x 10(4) x l(-1) for cardiopulmonary bypass surgery was considered too strict (41.4%). CONCLUSIONS: These guidelines for transfusions appear to be widely accepted. The most dominant complaint was the inadequacy of the guidelines for rapid massive bleeding.     

Concentration-dependent effect of hypocalcaemia on mortality of patients with critical bleeding requiring massive transfusion: a cohort study

Mortality of patients with critical bleeding requiring massive transfusion is high. Although hypothermia, acidosis and coagulopathy have been well described as important determinants of mortality in patients with critical bleeding requiring massive transfusion, the risk factors and outcome associated with hypocalcaemia in these patients remain uncertain. This cohort study assessed the relationship between the lowest ionised calcium concentration during the 24-hour period of critical bleeding and the hospital mortality of 352 consecutive patients, while adjusting for diagnosis, acidosis, coagulation results, transfusion requirements and use of recombinant factor VIIa. Hypocalcaemia was common (mean concentrations 0.77 mmol/l, SD 0.19) and had a linear; concentration-dependent relationship with mortality (odds ratio [OR] 1.25 per 0.1 mmol/l decrement, 95% confidence interval [CI]: 1.04 to 1.52; P = 0.02). Hypocalcaemia accounted for 12.5% of the variability and was more important than the lowest fibrinogen concentrations (10.8%), acidosis (7.9%) and lowest platelet counts (7.7%) in predicting hospital mortality. The amount of fresh frozen plasma transfused (OR 1.09 per unit, 95% CI: 1.02 to 1.17; P = 0.02) and acidosis (OR 1.45 per 0.1 decrement, 95% CI: 1.19 to 1.72; P = 0.01) were associated with the occurrence of severe hypocalcaemia (< 0.8 mmol/l). In conclusion, ionised calcium concentrations had an inverse concentration-dependent relationship with mortality of patients with critical bleeding requiring massive transfusion. Both acidosis and the amount of fresh frozen plasma transfused were the main risk factors for severe hypocalcaemia. Further research is needed to determine whether preventing ionised hypocalcaemia can reduce mortality of patients with critical bleeding requiring massive transfusion.     

Clopidogrel-related refractory bleeding after coronary artery bypass graft surgery: a rationale for the use of coagulation factor concentrates?

Clopidogrel, an irreversible ADP-receptor antagonist, inhibits platelet aggregation mediated by reduced activation of glycoprotein receptor IIb/IIIa. Clopidogrel in combination with aspirin has been shown to be superior to aspirin alone for treating unstable angina, but clopidogrel recipients have shown increases in blood loss, transfusion requirements, and rate of reoperation after cardiac surgery. We describe a patient who had taken clopidogrel 75 mg daily until the day prior to coronary artery bypass graft surgery. Severe postoperative bleeding developed and was refractory to conventional hemostatic therapy consisting of 19 units of packed red blood cell concentrates, 16 of fresh frozen plasma, 8 of platelet apheresis concentrates plus high-dose treatment with aprotinin (500.000 kallikrein-inhibiting units/h) and administration of 0.3 microg/kg 1-deamino-8-D-arginine vasopressin (DDAVP). Two reoperations were performed, but surgical hemostasis was not achieved, so 100 microg/kg recombinant activated factor VII was applied to generate sufficient thrombin to stop the bleeding. This treatment approach reduced the bleeding. Then, to promote clot formation and firmness, 2 g of fibrinogen and 1250 IU of factor XIII were administered, and the bleeding finally stopped. No further transfusions were required, and the patient was discharged from the hospital on day 10 after the operation. This case suggests that in clopidogrel-related bleeding refractory to conventional hemostatic therapy, hemostasis may be achieved by a stepwise administration of coagulation factor concentrates.     

Coagulation monitoring during extracorporeal membrane oxygenation: the role of thrombelastography

Patients undergoing extracorporeal membrane oxygenation (ECMO) are at an increased risk for developing coagulopathies due to the adverse effects of extracorporeal circulation on the hemostatic mechanism. Methods of determining causative factors of bleeding diathesis are often inconsistent and non-specific. ECMO patients require aggressive transfusion therapy with autogenic blood products to stabilize and maintain hemostasis. The present study evaluated the coagulation status of newborn patients undergoing ECMO therapy, using a viscoelastic monitor (Thrombelastograph -TEG) that measures functional aspects of clot development and stabilization. Seventeen neonatal patients undergoing ECMO for severe respiratory dysfunction were entered into this study. Serial blood samples were obtained and routine coagulation assessment including fibrinogen concentration, platelet count and ionized calcium was performed. In addition, fibrin(ogen) degradation products (FDP), d-Dimers, antithrombin III and plasma free hemoglobin were measured. Transfusion indicators were established and total transfusion requirements recorded. TEG profiles were determined with the use of heparinase, an enzyme that degrades heparin but has little effect on other coagulation factors. The most commonly encountered complication was hemorrhaging which was diagnosed by laboratory and clinical assessment in 11 of 17 patients. Transfusion requirements (measured in ml/kg/ECMO hour) were the following: packed red blood cells--1.34 +/- 0.5; platelets--0.71 +/- 0.57; fresh frozen plasma--0.09 +/- 0.12; cryoprecipitate 0.05 +/- 0.05. Thrombelastograph profiles reflected hemostatic conditions that ranged from severe coagulopathies (DIC) to hypercoagulability. Interpretation of TEG profiles identified hemostatic abnormalities in 57 of 101 profiles (46.5%), with the most common etiology related to platelet dysfunction.(ABSTRACT TRUNCATED AT 250 WORDS)     

Agreements between the prothrombin times of blood treated In Vitro with heparinase during cardiopulmonary bypass (CPB) and blood sampled after CPB and systemic protamine

The prothrombin time (PT) is useful for identifying coagulation factor deficits after cardiopulmonary bypass (CPB). However, long processing times and the need for fresh frozen plasma (FFP) to be thawed cause delays in factor replacement. We hypothesized that, by treating with heparinase, blood sampled toward the end of CPB can provide PT results that help to determine the requirement for FFP after CPB. Laboratory delays can be eliminated with point-of-care monitors. We studied 158 adults undergoing nonemergent cardiac surgery. Blood taken before separation from CPB was mixed with heparinase, and PT was measured in the laboratory with a HemoTec timer. Agreements between these results and laboratory measurements of blood taken after systemic protamine were compared by using Bland and Altman plots with the threshold of +/-1.0 s. We found that the laboratory PT measurements during CPB versus after CPB were compara-ble, but the limits of agreement exceeded these thresholds. Similarly, there was unsatisfactory agreement between the HemoTec and laboratory PT results measured before, during, and after CPB. For each PT measured during CPB, the corresponding confidence interval for the postprotamine PT was calculated. During CPB, a laboratory PT of < or =16 s or > or =18 s suggests a > or =83% or > or =93% probability of not requiring or potentially requiring, respectively, FFP after CPB. We conclude that the majority of PT measurements obtained from blood taken before weaning from CPB and treated in vitro with heparinase was associated with a high probability of whether or not FFP would be needed after CPB. IMPLICATIONS: Coagulation dysfunction after cardiopulmonary bypass may contribute to bleeding. Obtaining coagulation tests and fresh frozen plasma requires time and delays treatment in patients who need fresh frozen plasma. We have devised a technique to provide early estimation of postbypass coagulation status.     

Gerinnungsmanagement beim Polytrauma

Hemorrhage after traumatic injury results in coagulopathy which only worsens the situation. This coagulopathy is caused by depletion and dilution of clotting factors and platelets, increased fibrinolytic activity, hypothermia, metabolic changes and anemia. The effect of synthetic colloids used for compensating the blood loss, further aggravates the situation through their specific action on the hemostatic system. Bedside coagulation monitoring permits relevant impairment of the coagulation system to be detected very early and the efficacy of the hemostatic therapy to be controlled directly. Administration of fresh frozen plasma (FFP), platelet concentrates and antifibrinolytic agents is essential for restoring the impaired coagulation system in trauma patients. Clotting factor concentrates should be administered if coagulopathy is based on diagnosed depletion of clotting factors, if FFP is not available and if transfusion of FFP is insufficient to treat the coagulopathy. Recombined FVIIa is frequently employed during severe bleeding which could not be treated by conventional methods but the results of on-going clinical trials are not yet available.     

Using reagent-supported thromboelastometry (ROTEM((R))) to monitor haemostatic changes in congenital heart surgery employing deep hypothermic circulatory arrest

Objective: Cardiac surgery employing cardiopulmonary bypass (CPB) and deep hypothermic circulatory arrest (DHCA) can induce coagulation disturbances and bleeding complications that may be especially severe in infants. A better understanding of the coagulopathy and a quick method for its evaluation would be helpful in the management of patients exposed to CPB and DHCA. This study aimed to monitor coagulation defects in congenital heart surgery using rotational thromboelastometry (ROTEM((R))), standard coagulation tests and platelet flow cytometry. Methods: The study comprised 10 infants undergoing surgery for congenital heart disease on CPB and DHCA. Blood was sampled at skin incision, after heparinisation during CPB (directly pre- and directly post-DHCA) and after protamine administration post-CPB. ROTEM((R)) using different reagents including a heparinase-containing assay to evaluate coagulation during heparinisation, APTT and INR, and flow cytometry to evaluate platelet activation were performed. Results: During CPB, the ROTEM((R)) indicated CPB-induced clotting factor depletion and platelet dysfunction that persisted after CPB and heparin neutralisation. ROTEM((R)) results were available within 15min and therefore much faster than standard tests. ROTEM((R))-guided specific blood product treatment resulted in satisfactory coagulatory function. The highest degree of platelet activation was found directly after DHCA. Conclusions: A major benefit of ROTEM((R)) is the quick detection of a developing coagulopathy already during CPB. ROTEM((R)) guides quick and specific blood product treatment after CPB, which may decrease bleeding complications in cardiac surgery. The finding of maximal platelet activation directly after DHCA suggests that not only CPB but also hypothermia activates platelets in vivo, thereby contributing to platelet dysfunction.