Fibrinogen but not factor XIII deficiency is associated with bleeding after craniotomy.

BACKGROUND: Postoperative haemorrhage in neurosurgery is associated with significant morbidity and mortality. There is controversy whether or not factor XIII (FXIII) deficiency leads to bleeding complications after craniotomy. Decreased fibrinogen levels have been associated with an increased incidence of bleeding complications in cardiac and orthopaedic surgery. The aim of this study was to assess perioperative fibrinogen and FXIII levels in patients undergoing elective intracranial surgery with and without severe bleeding events. METHODS: Perioperative FXIII and fibrinogen levels were prospectively assessed in 290 patients undergoing elective craniotomy. Patients were divided into two groups according to the presence or absence of severe bleeding requiring surgical revision. Coagulation test results of these groups were compared using Student's t-test. RESULTS: The incidence of postoperative severe bleeding was 2.4%. No differences in FXIII levels were observed, but postoperative fibrinogen levels were significantly lower in patients suffering from postoperative haematoma compared with those without postoperative intracranial bleeding complications [237 mg dl(-1) (standard deviation, SD 86) vs 170 mg dl(-1) (SD 35), P=0.03]. The odds ratio for postoperative haematoma in patients with a postoperative fibrinogen level below 200 mg dl(-1) was 10.02 (confidence interval: 1.19-84.40, P=0.03). CONCLUSIONS: This study emphasizes the role of fibrinogen as potentially modifiable risk factor for perioperative bleeding in intracranial surgery. Future randomized controlled trials will be essential to identify patients who might benefit from fibrinogen substitution during neurosurgical procedures.

Monitoring of unfractionated heparin with rotational thrombelastometry using the prothrombinase-induced clotting time reagent (PiCT®).

PURPOSE: To achieve sufficient and safe anticoagulation with unfractionated heparin (UFH) a close and reliable drug monitoring is necessary. In general, the activated partial thromboplastin time (APTT) is used for this purpose. In acute phase response, however, the APTT test procedure might be unreliable e.g. with false low results in the presence of elevated factor VIII. In this so called heparin resistance, measurement of anti-Xa activity is recommended over APTT to avoid potentially harmful dose escalation. A combination of anti-Xa measurement and global hemostatic testing with ROTEM® employing the anti-Xa sensitive PiCT® reagent showed high correlation with enoxaparin levels. This test modification could also be suitable for monitoring UFH. Aim of the study was to evaluate the correlation between PiCT®-ROTEM® and levels of UFH. METHODS: In this in-vitro study blood samples from healthy volunteers were spiked with UFH and subjected to different ROTEM® tests. RESULTS: There was a linear correlation between UFH level and clotting time (CT) in the PiCT®-ROTEM® test with an excellent correlation coefficient of 0.92. Additional endpoints showed similar results (PiCT®-ROTEM® MaxVel r = -0.85 and PiCT®-ROTEM® t_MaxVel r = 0.88). CONCLUSIONS: As a point-of-care applicable tool ROTEM® is immediately at hand. If further clinical studies confirm sensitivity in heparin resistance, PiCT®-ROTEM® could permit rapid UFH dose adjustments especially required in critical illness with acute phase response.

Effect of the carrier solution for hydroxyethyl starch on platelet aggregation and clot formation.

BACKGROUND: Hydroxyethyl starch (HES) solutions alter blood coagulation, mainly platelet function and fibrinogen polymerization. Haemostasis can also be impaired by dilutional-hyperchloraemic acidosis induced by the HES carrier solution. We hypothesized that a saline-based tetrastarch carrier solution impairs parameters of blood coagulation more than a balanced carrier solution. METHODS: The study was designed as a prospective, double-blinded, randomized, cross-over trial in healthy male volunteers. At intervals of at least 10 days, 13 subjects received 20 ml kg(-1) of balanced or saline-based tetrastarch over 2 h. Blood was subjected to blood gas analysis, assessment of platelet function [with multiple electrode aggregometry (MEA)], and clot formation (with rotational thrombelastometry). RESULTS: Maximum aggregation in response to adenosine diphosphate (ADP) decreased after saline-based HES infusion, but not after balanced solution-based HES infusion. ADP-induced platelet aggregation was significantly lower after saline-based HES compared with baseline (21%; P<0.025) and compared with balanced solution-based HES (17%; P<0.025). There were no significant changes in platelet aggregation induced by thrombin receptor-activating peptide and in any parameter of rotational thrombelastometry. Chloride concentrations were significantly higher after saline-based HES compared with balanced solution-based HES. CONCLUSIONS: The carrier solution for HES up to 20 ml kg(-1) had little impact on platelet aggregation or clot formation as assessed by MEA and rotational thrombelastometry, respectively. Further clinical studies are required to verify this finding in patients and to correlate results of whole blood aggregometry and rotational thrombelastometry with perioperative bleeding and transfusion requirements.

Perioperative treatment algorithm for bleeding burn patients reduces allogeneic blood product requirements.

BACKGROUND: Surgical excision of burn wounds is often associated with severe bleeding. Timely and targeted correction of coagulopathy reduces transfusion requirements and improves survival in trauma victims. We hypothesized that rapid correction of coagulopathy after a treatment algorithm based on point-of-care viscoelastic coagulation testing would decrease allogeneic blood product transfusions during surgical excision of burn wounds. METHODS: Thirty consecutive patients undergoing surgical excision of burn wounds were enrolled into this prospective, randomized, controlled, single-centre study. In the control group, coagulation management was performed according to the clinicians' discretion. For the algorithm group, we standardized treatment based on the Austrian recommendation for the management of trauma-induced coagulopathy using point-of-care rotational thromboelastometry (ROTEM(®)). The main outcome parameter was the cumulative number of allogeneic blood units transfused on the day of surgery. RESULTS: The difference between the groups regarding the cumulative use of allogeneic blood products was highly significant with 3.0 (1.3-5.5) blood products in the algorithm group compared with 9.0 (6.0-12.3) in the control group [median (inter-quartile range); P=0.002]. No plasma was administered in the algorithm group compared with 5.0 (1.5-7.5) units overall in the control group (P<0.001). Fibrinogen concentrate administration was not significantly different between the groups (P=0.89). Tranexamic acid was not administered. CONCLUSIONS: The significant reduction in allogeneic blood product requirements during surgical burn wound excision is a prospective proof of concept that a bleeding management algorithm based on thromboelastometry is efficacious. Hypofibrinogenaemia and hyperfibrinolysis are not significant pathomechanisms of bleeding in this setting and ROTEM(®) helps to avoid unnecessary interventions.

Coagulation Day 2010: an Austrian survey on the routine of thromboprophylaxis in intensive care.

PURPOSE: Venous thromboembolism (VTE) is a common but often overlooked life-threatening complication of critical illness. The aim of this cross-sectional survey was to assess current practice of thromboprophylaxis as well as adherence to international guidelines. METHODS: After ethics committee approval, all intensive care units in Austrian hospitals treating adult patients were invited to participate in this web-based survey. Anonymized data on each patient treated at the participating intensive care units on Coagulation Day 2010 were collected using an electronic case report form. Risk assessment, choice and monitoring of anticoagulants, means of mechanical prophylaxis, and demographic data were recorded. RESULTS: Data from 325 critically ill patients were collected. Patients had a median of four risk factors for thrombosis and 6 % suffered from VTE. Of the 325 patients, 80 % received low molecular weight heparins subcutaneously, 10 % received unfractionated heparin intravenously, 1 % received alternative anticoagulants and 9 % received no pharmacological prophylaxis. Mechanical prophylaxis was used in 49 % with a predominant use of graduated compression stockings. In 39 % a combination of pharmacological and mechanical prophylaxis was applied and 5 % received no prophylaxis at all. Overall guideline adherence was 40 % on Coagulation Day 2010. CONCLUSION: Current practice of thromboprophylaxis is predominantly based on the administration of low molecular weight heparins prescribed at rather arbitrary doses without a discernible relationship to drug monitoring, thromboembolic risk factors, vasopressor use or fluid balance. The use of mechanical prophylaxis, evaluation of risk scores and overall guideline adherence must be further encouraged by education, training and communication.

Point-of-care assessment of platelet aggregation in paediatric open heart surgery.

BACKGROUND: Congenital heart disease (CHD) is associated with complex coagulation abnormalities. Platelet aggregability has not been investigated in detail in children with acyanotic and cyanotic malformations undergoing open heart surgery. The method of whole-blood multiple electrode aggregometry (MEA) appears suitable for rapid platelet analysis in children, for example, because of small sample volumes. We investigated perioperative evolution of platelet aggregation by means of MEA in children with CHD. METHODS: Fifty children with acyanotic or cyanotic malformations were included in a prospective observational study. Laboratory testing was assessed before anaesthesia, and during and after surgery until the fifth postoperative day. MEA was performed in hirudin-anticoagulated blood using adenosine diphosphate (ADP), arachidonic acid, and thrombin receptor-activating peptide for platelet activation. Surgical variables, bleeding volumes, and transfusion requirements were documented during hospital stay. RESULTS: Mean platelet count was within the normal range in all patients with no intergroup differences. Before surgery, aggregation to all agonists was within the age-adjusted normal range in cyanotic children and was statistically significantly higher compared with acyanotic children. Platelet aggregation decreased significantly during surgery in both groups followed by a slow recovery not reaching baseline levels. Bleeding and platelet transfusions were higher in the cyanotic group. Transfusion requirements correlated with ADP-induced platelet aggregation. CONCLUSIONS: These results indicate higher blood loss, despite better platelet aggregation in cyanotic patients compared with acyanotic patients. MEA alone might not be suitable for predicting increased perioperative blood loss.

Intracranial pressure-alterations during controlled intramedullary reaming of femoral fractures: an animal study.

Reaming during intramedullary nailing increases the intramedullary pressure (IMP) and can cause fat intravasation and subsequently lead to pulmonary dysfunction, especially in polytraumatized patients with lung contusion as well as increases in intracranial pressure (ICP).ICP changes were measured in two groups consisting of 12 sheep each with either a fractured or intact femur. The animals were exposed to haemorrhagic shock and were resuscitated by autoinfusion. Transverse midshaft fractures were created bilaterally in one group before reaming of both femoral shafts. Controlled reaming was performed at 15 and 50 mm/s driving speed (DS) and at 150 and 450 revolutions per minute (RPM) with a reaming control system using AO-Reamers. Fat intravasation was measured by transoesophageal sonography (TES) and Gurd test. ICP monitoring was performed with a piezo-electric epidural catheter. Haemodynamic and respiratory parameters, ICP, and cerebral perfusion pressure were measured continuously. High DS and low RPM caused higher IMP and ICP increases in both groups. Significantly higher microemboli were observed in TES in the fractured group as compared to the unfractured group with the same reaming parameters (P=0.021). However, the existence of a femoral fracture did not show a significant influence on changes in ICP (P-value=0.057). Reaming should be performed at a low DS and high RPM to minimize the risk of fat intravasation and the subsequent ICP increase.