Rational and timely haemostatic interventions following cardiac surgery - coagulation factor concentrates or blood bank products.

BACKGROUND: Cardiac surgery may cause a serious coagulopathy leading to increased risk of bleeding and transfusion demands. Blood bank products are commonly first line haemostatic intervention, but has been associated with hazardous side effect. Coagulation factor concentrates may be a more efficient, predictable, and potentially a safer treatment, although prospective clinical trials are needed to further explore these hypotheses. This study investigated the haemostatic potential of ex vivo supplementation of coagulation factor concentrates versus blood bank products on blood samples drawn from patients undergoing cardiac surgery. METHODS: 30 adults were prospectively enrolled (mean age=63.9, females=27%). Ex vivo haemostatic interventions (monotherapy or combinations) were performed in whole blood taken immediately after surgery and two hours postoperatively. Fresh-frozen plasma, platelets, cryoprecipitate, fibrinogen concentrate, prothrombin complex concentrate (PCC), and recombinant FVIIa (rFVIIa) were investigated. The haemostatic effect was evaluated using whole blood thromboelastometry parameters, as well as by thrombin generation. RESULTS: Immediately after surgery the compromised maximum clot firmness was corrected by monotherapy with fibrinogen or platelets or combination therapy with fibrinogen. At two hours postoperatively the coagulation profile was further deranged as illustrated by a prolonged clotting time, a reduced maximum velocity and further diminished maximum clot firmness. The thrombin lagtime was progressively prolonged and both peak thrombin and endogenous thrombin potential were compromised. No monotherapy effectively corrected all haemostatic abnormalities. The most effective combinations were: fibrinogen+rFVIIa or fibrinogen+PCC. Blood bank products were not as effective in the correction of the coagulopathy. CONCLUSION: Coagulation factor concentrates appear to provide a more optimal haemostasis profile following cardiac surgery compared to blood bank products.

Temporal changes in clot lysis and clot stability following tranexamic acid in cardiac surgery.

: Cardiac surgery induces a multifactorial coagulopathy. Regular use of tranexamic acid (TXA) is becoming standard of care. Clinical challenges include selecting optimal dosing regimen and balancing the benefit versus risk of additional dosing with antifibrinolytics. The objective was to evaluate the effect of TXA by assessing kinetic properties of plasma clot formation, clot stability, and clot fibrinolysis. The study was a prospective case follow-up of 28 patients undergoing cardiac surgery (mean age 63.9 years, 29% women). Blood samples were analysed at seven time points during the first 48 h after surgery. All patients were treated with TXA, 2 g at start surgery, 1 g during extra corporeal circulation, and 1 g after reversal of heparin. An automated clot lysis assay using tissue factor and tissue plasminogen activator (tPA) was performed to evaluate clot formation, stability, and fibrinolysis. TXA protects against facilitated fibrinolysis and induces up to 13-fold increase in clot stability. All patients showed complete resistance to tPA-induced fibrinolysis during the first 6 h after cardiac surgery declining to 33% of patients at 48 h. Impaired renal function was associated with prolonged resistance to tPA-induced fibrinolysis. Despite inhibition of fibrinolysis with TXA, the overall clot stability declines and the kinetic properties of clot formation were impaired after cardiac surgery. TXA induces a multifold increase in clot resistance to fibrinolysis but does not affect clot formation or clot stability. Monitoring the level of resistance to fibrinolysis may prevent overdosing in particular in patients with impaired renal function.

Clinical phenotype in heterozygote and biallelic Bernard-Soulier syndrome--a case control study.

Bernard-Soulier syndrome (BSS) is a rare severe autosomal recessive bleeding disorder. To date heterozygous carriers of BSS mutations have not been shown to have bleeding symptoms. We assessed bleeding using a semi-quantitative questionnaire, platelet parameters, PFA-100 closure times, ristocetin response, GP Ib/IX expression and VWF antigen in 14 BSS patients, 30 heterozygote carriers for related mutations and 29 controls. Eight mutations in GP1BA, GP1BB or GP9 were identified including four previously unknown pathogenic mutations. Subjects with BSS reported markedly more mucocutaneous bleeding than controls. Increased bleeding was also observed in heterozygotes. Compared to controls, patients with BSS had lower optical platelet counts (P < 0.001), CD61-platelet counts (P < 0.001) and higher mean platelet volume (17.7 vs. 7.8 fL, P < 0.001) and ristocetin response and closure times were unmeasurable. Heterozygotes had higher MPV (9.7 fL, P < 0.001) and lower platelet counts (P < 0.001) than controls but response to ristocetin and closure times were normal. The VWF was elevated in both BSS and in heterozygotes (P = 0.005). We conclude that heterozygotes for BSS mutations have lower platelet counts than controls and show a bleeding phenotype albeit much milder than in BSS. Both patients with BSS and heterozygote carriers of pathogenic mutations have raised VWF.

Complementary effect of fibrinogen and rFVIIa on clotting ex vivo in Bernard-Soulier syndrome and combined use during three deliveries.

Women with Bernard-Soulier syndrome (BSS) are considered to be at high risk of serious bleeding during childbirth. Due to the frequently occurring platelet transfusion refractoriness, alternative prophylactic therapy is required. Using rotational thromboelastometry, we evaluated the whole blood coagulation profile of a pregnant woman with BSS before and after spiking ex vivo with different concentrations of recombinant activated factor VII (rFVIIa) and fibrinogen. As experiments suggested improved clotting with clinically applicable concentrations of both agents in a complementary manner, the findings were confirmed on blood from a non-pregnant woman and three men suffering from BSS. During delivery, bleeding refractory to platelets occurred and immediately following delivery she received both rFVIIa and fibrinogen intravenously. Immediate cessation of bleeding occurred, and no postpartum hemorrhage was seen. Another woman with BSS later also received the same rFVIIa and fibrinogen treatment prophylactically after delivery without any postpartum bleeding. Eventually, the first woman during her second delivery received the same treatment again prophylactically without any bleeding. No side effects were observed during these three deliveries. Our observations suggest that rFVIIa combined with fibrinogen may provide a beneficial clinical hemostatic effect partly by separate but complementary mechanisms.

Identification and characterisation of mutations associated with von Willebrand disease in a Turkish patient cohort.

Several cohort studies have investigated the molecular basis of von Willebrand disease (VWD); however, these have mostly focused on European and North American populations. This study aimed to investigate mutation spectrum in 26 index cases (IC) from Turkey diagnosed with all three VWD types, the majority (73%) with parents who were knowingly related. IC were screened for mutations using multiplex ligation-dependent probe amplification and analysis of all von Willebrand factor gene (VWF) exons and exon/intron boundaries. Selected missense mutations were expressed in vitro. Candidate VWF mutations were identified in 25 of 26 IC and included propeptide missense mutations in four IC (two resulting in type 1 and two in recessive 2A), all influencing VWF expression in vitro. Four missense mutations, a nonsense mutation and a small in-frame insertion resulting in type 2A were also identified. Of 15 type 3 VWD IC, 13 were homozygous and two compound heterozygous for 14 candidate mutations predicted to result in lack of expression and two propeptide missense changes. Identification of intronic breakpoints of an exon 17-18 deletion suggested that the mutation resulted from non-homologous end joining. This study provides further insight into the pathogenesis of VWD in a population with a high degree of consanguineous partnerships.

Prophylaxis in congenital factor VII deficiency: indications, efficacy and safety. Results from the Seven Treatment Evaluation Registry (STER).

Because of the very short half-life of factor VII, prophylaxis in factor VII deficiency is considered a difficult endeavor. The clinical efficacy and safety of prophylactic regimens, and indications for their use, were evaluated in factor VII-deficient patients in the Seven Treatment Evaluation Registry. Prophylaxis data (38 courses) were analyzed from 34 patients with severe factor VII deficiency (<1-45 years of age, 21 female). Severest phenotypes (central nervous system, gastrointestinal, joint bleeding episodes) were highly prevalent. Twenty-one patients received recombinant activated factor VII (24 courses), four received plasma-derived factor VII, and ten received fresh frozen plasma. Prophylactic schedules clustered into "frequent" courses (three times weekly, n=23) and "infrequent" courses (≤ 2 times weekly, n=15). Excluding courses for menorrhagia, "frequent" and "infrequent" courses produced 18/23 (78%) and 5/12 (41%) "excellent" outcomes, respectively; relative risk, 1.88; 95% confidence interval, 0.93-3.79; P=0.079. Long term prophylaxis lasted from 1 to >10 years. No thrombosis or new inhibitors occurred. In conclusion, a subset of patients with factor VII deficiency needed prophylaxis because of severe bleeding. Recombinant activated factor VII schedules based on "frequent" administrations (three times weekly) and a 90 µg/kg total weekly dose were effective. These data provide a rationale for long-term, safe prophylaxis in factor VII deficiency.

Replacement therapy for bleeding episodes in factor VII deficiency. A prospective evaluation.

Patients with inherited factor VII (FVII) deficiency display different clinical phenotypes requiring ad hoc management. This study evaluated treatments for spontaneous and traumatic bleeding using data from the Seven Treatment Evaluation Registry (STER). One-hundred one bleeds were analysed in 75 patients (41 females; FVII coagulant activity <1-20%). Bleeds were grouped as haemarthroses (n=30), muscle/subcutaneous haematomas (n=16), epistaxis (n=12), gum bleeding (n=13), menorrhagia (n=16), central nervous system (CNS; n=9), gastrointestinal (GI; n=2) and other (n=3). Of 93 evaluable episodes, 76 were treated with recombinant, activated FVII (rFVIIa), eight with fresh frozen plasma (FFP), seven with plasma-derived FVII (pdFVII) and two with prothrombin-complex concentrates. One-day replacement therapy resulted in very favourable outcomes in haemarthroses, and was successful in muscle/subcutaneous haematomas, epistaxis and gum bleeding. For menorrhagia, single- or multiple-dose schedules led to favourable outcomes. No thrombosis occurred; two inhibitors were detected in two repeatedly treated patients (one post-rFVIIa, one post-pdFVII). In FVII deficiency, most bleeds were successfully treated with single 'intermediate' doses (median 60 µg/kg) of rFVIIa. For the most severe bleeds (CNS, GI) short- or long-term prophylaxis may be optimal.

Combination of recombinant factor VIIa and fibrinogen corrects clot formation in primary immune thrombocytopenia at very low platelet counts.

Haemostatic treatment modalities alternative to platelet transfusion are desirable to control serious acute bleeds in primary immune thrombocytopenia (ITP). This study challenged the hypothesis that recombinant activated factor VII (rFVIIa) combined with fibrinogen concentrate may correct whole blood (WB) clot formation in ITP. Blood from ITP patients (n = 12) was drawn into tubes containing 3·2% citrate and corn trypsin inhibitor 18·3 µg/ml. WB [mean platelet count 22 × 10(9) /l (range 0-42)] was spiked in vitro with buffer, donor platelets (+40 × 10(9) /l), rFVIIa (1 or 4 µg/ml), fibrinogen (1 or 3 mg/ml), or combinations of rFVIIa and fibrinogen. Coagulation profiles were recorded by tissue factor (0·03 pmol/l) activated thromboelastometry. Coagulation in ITP was characterized by a prolonged clotting time (CT, 1490 s (mean)) and a low maximum velocity (MaxVel, 3·4 mm × 100/s) and maximum clot firmness (MCF, 38·2 mm). Fibrinogen showed no haemostatic effect, whereas rFVIIa reduced the CT and increased the MaxVel. The combination of fibrinogen and rFVIIa revealed a significant synergistic effect, improving all parameters (CT 794 s, MaxVel 7·9 mm × 100/s, MCF 50·7 mm) even at very low platelet counts. These data suggest that rFVIIa combined with fibrinogen corrects the coagulopathy of ITP even at very low platelet counts, and may represent an alternative to platelet transfusion.

Efficacy and safety of prophylaxis with once-weekly BAY 79-4980 compared with thrice-weekly rFVIII-FS in haemophilia A patients. A randomised, active-controlled, double-blind study.

The benefits of prophylaxis of haemophilia A patients regarding joint health and quality-of-life are well established. However, adherence to an up to every-other-day infusion regimen is a barrier to widespread adoption of prophylaxis. BAY 79-4980 is an investigational drug consisting of rFVIII-FS (sucrose-formulated recombinant FVIII) reconstituted with liposome solvent. Previous clinical studies showed extended protection from bleeding after a single injection of BAY 79-4980 (13.3 ± 6.2 days) compared with rFVIII-FS (7.2 ± 1.7 days). The effect of once-a-week prophylaxis with BAY 79-4980 (35 IU/kg) compared with three times-per-week rFVIII-FS (25 IU/kg) in previously treated, severe haemophilia A patients was evaluated in a 52-week, double-blind, two-arm, randomised, controlled study. The primary and secondary endpoints were protection from total bleeds and joint bleeds, respectively. Short- and long-term safety and tolerability of BAY 79-4980 including effects on lipid levels were assessed. A total of 139 and 131 subjects were evaluable for safety and efficacy analyses, respectively. A large difference in efficacy between treatment groups was observed with 72.1% (49/68) in the rFVIII-FS control group demonstrating <9 bleeds/year compared with 38.1% (24/63) of BAY 79-4980-treated subjects. A similar difference was seen in annualised joint bleeds, with 43 subjects (63.2%) in the control group demonstrating <5 joint bleeds/year compared with 24 subjects (38.1%) treated with BAY 79-4980. The distribution of bleeds seven days post-prophylactic treatment with BAY 79-4980 showed that 61% of bleeds occurred after day 4 post dosing. There were no safety concerns identified. The investigational treatment arm was prematurely discontinued due to failure to achieve the primary endpoint.

Coagulation and fibrinolytic disturbances are related to carotid intima thickness and arterial blood pressure in Turner syndrome.

OBJECTIVE: Turner syndrome (TS) is characterized by growth retardation, hypogonadism and a high risk of cardiovascular complications and atherosclerosis; case reports suggest that thrombo-embolic complications may be present. DESIGN: Cross-sectional study. PATIENTS: Sixty women with TS. MEASUREMENTS: We characterized the activities of the haemostatic system, elucidated by the assessment of a panel of clotting factors and thrombosis risk factors and related these findings to carotid intima thickness (CIMT) and blood pressure. RESULTS: Most (81%) received hormone replacement therapy. The medians of all measured factors and inflammatory parameters were not different from normative data, but many cases displayed values of C-reactive protein (CRP) (40%), fibrinogen (15%), fibrin D-dimer (15%), factor VIII (25%), von Willebrand factor (vWF) (15%), cholesterol and liver parameters that were greater than normative limits. CRP, fibrinogen, vWF, factor VIII and liver parameters were highly and positively correlated. Haemostatic variables were positively related to both CIMT and blood pressure. The Factor V Leiden G1691A gene polymorphism heterozygosity was detected in 12·5%. CONCLUSION: We describe a significant proportion of individual TS females having high levels of vWF, factor VIII, fibrinogen and CRP (15-40%) and an increased frequency of the Leiden mutation, with important associations with CIMT and blood pressure, suggesting that a subset of TS may have an unfavourable haemostatic balance, which may contribute to the increased risk of premature ischaemic heart disease and possibly increase the risk of deep venous and portal vein thrombosis.

Parallel use of by-passing agents in haemophilia with inhibitors: a critical review.

In the absence of new outbreaks of transfusion-related infections, the occurrence of neutralizing antibodies currently remains the most prominent complication in haemophilia. Coagulation factor products that may circumvent the inadequate activation of factor X in classical haemophilia, often referred to as bypassing agents, have demonstrated a high degree of efficacy. A smaller number of patients have been described in whom either bypassing agent, or both, demonstrate diminished efficacy. In those cases, the use of both bypassing agents in parallel was attempted, either using simultaneous (combined) or alternating (sequential) infusion of the two drugs, reportedly with successful haemostasis. We speculated whether such treatment might cause thromboembolism. A thorough literature search disclosed 17 reports regarding the parallel use of bypassing agents in the same bleeding episode in 49 patients; reporting nine patients with acquired haemophilia and forty patients with congenital haemophilia with inhibitors. Notable incidences of thromboembolic manifestations were observed: in nine patients with acquired haemophilia, five and in 40 patients with congenital haemophilia five suffered from significant thrombotic complications, and overall four cases were fatal. Although efficacy of parallel treatment was reported excellent in most cases, thromboembolism is rare in haemophilia and parallel treatment with activated prothrombin complex concentrate and activated recombinant human factor VII appears to increase the risk of thrombosis in these patients.

Diagnostic performance and therapeutic consequence of thromboelastometry activated by kaolin versus a panel of specific reagents.

BACKGROUND: Thromboelastography/metry (TEG®; Haemoscope, Niles, IL/ROTEM®; Tem International GmbH, Munich, Germany) is increasingly used to guide transfusion therapy. This study investigated the diagnostic performance and therapeutic consequence of using kaolin-activated whole blood compared with a panel of specific TEM®-reagents to distinguish: dilutional coagulopathy, thrombocytopenia, hyperfibrinolysis, and heparinization. METHODS: Blood was drawn from 11 healthy volunteers. Dilutional coagulopathy was generated by 50% dilution with hydroxyethyl starch 130/0.4 whereas thrombocytopenia (mean platelet count 20 ×109/l) was induced using a validated model. Hyperfibrinolysis and heparin contamination were generated by tissue plasminogen activator 2 nM and unfractionated heparin 0.1U/ml, respectively. Coagulation tests were run on ROTEM® delta. RESULTS: Kaolin-activated whole blood showed no differences between dilutional coagulopathy and thrombocytopenia (mean clotting time 450 s vs. 516 s, α-angle 47.1° vs. 41.5°, maximum clot firmness 35.0 mm vs. 34.2 mm, all P values ≥0.14). Hyperfibrinolysis specifically disclosed an increased maximum lysis (median: 100%, all P values less than 0.001), and heparin induced a distinctly prolonged clotting time (2283 s, all P values less than 0.02). The coagulopathies were readily distinguishable using a panel of TEM-reagents. In particular, dilutional coagulopathy was separated from thrombocytopenia using FIBTEM (maximum clot firmness 1.9 mm vs. 11.2 mm, P < 0.001). The run time of analysis to achieve diagnostic data was shorter applying a panel of TEM-reagents. A transfusion algorithm based on kaolin suggested platelets in case of dilutional coagulopathy, whereas an algorithm applying TEM-reagents suggested fibrinogen. CONCLUSION: Monoanalysis with kaolin was unable to distinguish coagulopathies caused by dilution from that of thrombocytopenia. Algorithms based on the use of kaolin may lead to unnecessary transfusion with platelets, whereas the application of TEM-reagents may result in goal-directed fibrinogen substitution.

Recombinant, activated factor VII for surgery in factor VII deficiency: a prospective evaluation - the surgical STER.

Excessive bleeding represents a major complication of surgical interventions and its control is especially relevant in patients with Congenital Bleeding Disorders (CBD). In factor VII (FVII) deficiency, scanty data on surgery is available to guide treatment strategies. The STER (Seven Treatment Evaluation Registry) is a multi-centre, prospective, observational, web-based study protocol providing the frame for a structured and detailed data collection. Inhibitor occurrence was checked in a centralized fashion. Forty-one surgical operations (24 'major' and 17 'minor') were performed in 34 subjects with a carefully characterized FVII deficiency under the coverage of recombinant activated Factor VII (rFVIIa). Bleeding occurred during three major interventions of orthopaedic surgery, but rFVIIa was given at very low dose in each case. An antibody to FVII was observed in one patient who underwent a multiple dental extraction. No thromboses were reported during the 30-d follow up period. Replacement therapy with rFVIIa proved effective when suitable doses were used, which, during the period of maximum bleeding risk (the day of operation), were calculated (Receiver Operated Characteristic analysis) to be of at least 13 µg/kg/body weight per single dose and no less than three administrations. This indication is important especially in the case of major surgery.

The impact of bleeding history, von Willebrand factor and PFA-100(®) on the diagnosis of type 1 von Willebrand disease: results from the European study MCMDM-1VWD.

The relationships between the Platelet Function Analyzer (PFA)-100 and von Willebrand factor (VWF) levels and bleeding score (BS) were evaluated within a multicentre project on Molecular and Clinical Markers for the Diagnosis and Management of type 1 von Willebrand disease (MCMDM-1VWD). PFA-100 closure time, either with epinephrine (EPI) or adenosine diphosphate (ADP)-cartridges, was measured in 107 index cases, 105 affected and 71 unaffected family members, and 79 healthy controls. By regression analysis VWF levels were strongly related to both closure times, with a non-linear progression. In a multiple stepwise regression model, age- and sex-adjusted PFA-100 ADP and VWF ristocetin cofactor activity (VWF:RCo) were independently associated with BS. Most of the variation of BS was predicted by PFA-100 ADP and VWF:RCo alone. In the subgroup of patients with subtle abnormalities of the multimeric pattern, VWF was invariably reduced and closure time prolonged in almost all of them. Neither PFA-100 ADP nor EPI closure times appeared to significantly improve the diagnostic capability of VWF antigen (VWF:Ag) measurement. Thus, in an unselected population a normal PFA-100 would be useful to exclude VWD, but whether it could replace the more specific VWF assay in patients with significant mucocutaneous bleeding symptoms remains to be investigated prospectively.

Consensus recommendations for the diagnosis and treatment of acquired hemophilia A.

BACKGROUND: Acquired hemophilia A (AHA) is a rare bleeding disorder caused by an autoantibody to coagulation factor (F) VIII. It is characterized by soft tissue bleeding in patients without a personal or family history of bleeding. Bleeding is variable, ranging from acute, life-threatening hemorrhage, with 9-22% mortality, to mild bleeding that requires no treatment. AHA usually presents to clinicians without prior experience of the disease, therefore diagnosis is frequently delayed and bleeds under treated. METHODS: Structured literature searches were used to support expert opinion in the development of recommendations for the management of patients with AHA. RESULTS: Immediate consultation with a hemophilia center experienced in the management of inhibitors is essential to ensure accurate diagnosis and appropriate treatment. The laboratory finding of prolonged activated partial thromboplastin time with normal prothrombin time is typical of AHA, and the diagnosis should be considered even in the absence of bleeding. The FVIII level and autoantibody titer are not reliable predictors of bleeding risk or response to treatment. Most patients with AHA are elderly; comorbidities and underlying conditions found in 50% of patients often influence the clinical picture. Initial treatment involves the control of acute bleeding with bypassing agents. Immunosuppressive treatment to eradicate the FVIII inhibitor should be started as soon as the diagnosis is confirmed to reduce the time the patient is at risk of bleeding. CONCLUSIONS: These recommendations aim to increase awareness of this disorder among clinicians in a wide range of specialties and provide practical advice on diagnosis and treatment.

Fibrinogen estimates are influenced by methods of measurement and hemodilution with colloid plasma expanders.

BACKGROUND: Measurement of plasma fibrinogen is often required in critically ill patients or massively bleeding patients being resuscitated with colloid plasma expander. This study aimed at evaluating different assays of plasma fibrinogen after in vitro dilution with commonly used plasma expanders and challenged the hypothesis that levels of fibrinogen are estimated significantly higher in plasma diluted with colloid plasma expander compared with isotonic saline. STUDY DESIGN AND METHODS: Fibrinogen measurements were established in plasma samples each diluted in vitro to 30 or 50% with isotonic saline, hydroxyethyl starch (HES) 130/0.4, and human albumin. Fibrinogen levels were assessed using an antigen determination, three photo-optical Clauss methods, one mechanical Clauss method, a prothrombin-derived method, and viscoelastic measurement through thromboelastometry. RESULTS: Measurement of fibrinogen levels was significantly different when performed on alternate analytical platforms. By 30 and 50% dilution with HES 130/0.4 coagulation analyzers using the photo-optical Clauss methods significantly overestimated levels of fibrinogen. Dilution with human albumin did not affect fibrinogen levels except from one analyzer by 50% dilution level. Viscoelastic measurement of fibrin polymerization was reduced at both dilution levels and appeared to reflect the impairment of fibrin polymerization induced by HES 130/0.4 and to a lesser extent human albumin. CONCLUSION: This study demonstrated that different automated coagulation analyzers revealed significantly different levels of fibrinogen. The presence of colloid plasma expander gave rise to erroneous high levels of fibrinogen returned from some coagulation analyzers employing the method of Clauss.

Evaluation of coagulation kinetics using thromboelastometry-methodologic influence of activator and test medium.

Renewed interest has arisen in the use of thromboelastography/thromboelastometry in evaluating coagulation kinetics. The test medium, type of activator, and its concentration may influence the interpretation of coagulation kinetics. This study aimed to investigate methodologic influences of activator and test medium on thromboelastometric parameters of coagulation kinetics. Dynamic clot formation was evaluated by thromboelastometry using whole blood (WB), platelet-rich plasma, or platelet-poor plasma employing different concentrations of extrinsic (tissue factor) and contact activator (synthasil) and with variable concentrations of phospholipids. Plasma samples displayed prolonged clot initiation and enhanced clot propagation compared with WB. Clot firmness was markedly reduced in platelet-poor plasma as compared with platelet-rich plasma and WB. Increasing concentration of activator shortened the clot initiation and increased the velocity of clot propagation, whereas terminal clot firmness remained unaffected. Platelets accelerated clot propagation and raised clot firmness. Phospholipids shortened the time of clot initiation and increased velocity of propagation, while clot firmness remained unchanged. Our results demonstrate that evaluation of coagulation kinetics using thromboelastometry varies according to the composition of the test medium, type, and concentration of activator, as well as the presence and concentration of phospholipids in the test reagent.