Common Coagulation Tests Research Articles

ダビガトラン過量服薬に対するイダルシズマブの静脈内投与：血漿中ダビガトラン濃度と血液凝固能の関連性(Intravenous idarucizumab for dabigatran overdose: association between plasma dabigatran concentration and coagulation profile)

要旨ダビガトランは直接トロンビンを阻害することで抗凝固作用を示す経口抗凝固薬であり，近年処方機会が急増している。過量内服症例における，血漿中ダビガトラン濃度および血液凝固能の推移に関するデータは不足している。腎機能障害のない，非弁膜症性心房細動をもつ71歳邦人女性が近医より処方されていたダビガトランを合計7,480mg自殺目的に過量内服し，当院に搬送された。過量内服4時間後の血漿中ダビガトラン濃度は4,217ng/mL（治療域濃度100～400ng/mL）であり，APTTは160.3秒，PT–INRは9.46であった。イダルシズマブ5g経静脈投与後，血漿中ダビガトラン濃度は経時的に低下し，それに伴いAPTTとPT–INRも正常化した。血漿中ダビガトラン濃度とAPTT（R2=0.9898），およびPT–INR（R2=0.9998）との間には強固な関連性が認められた。本症例は第9病日に後遺症なく独歩退院した。治療域の40倍の血漿中濃度を示すダビガトラン大量内服症例において，イダルシズマブは血漿中ダビガトラン濃度を安全に，かつ効果的に低下させた。また，血液凝固能は，血漿中ダビガトラン濃度を強固に反映した。本症例により，一般的な血液凝固能検査を用いることで，ダビガトランの血中薬物動態を推定できる可能性が示された。

Viscoelastic Hemostatic Assays for Orthopedic Trauma and Elective Procedures.

The application of viscoelastic hemostatic assays (VHAs) (e.g., thromboelastography (TEG) and rotational thromboelastometry (ROTEM)) in orthopedics is in its relative infancy when compared with other surgical fields. Fortunately, several recent studies describe the emerging use of VHAs to quickly and reliably analyze the real-time coagulation and fibrinolytic status in both orthopedic trauma and elective orthopedic surgery. Trauma-induced coagulopathy—a spectrum of abnormal coagulation phenotypes including clotting factor depletion, inadequate thrombin generation, platelet dysfunction, and dysregulated fibrinolysis—remains a potentially fatal complication in severely injured and/or hemorrhaging patients whose timely diagnosis and management are aided by the use of VHAs. Furthermore, VHAs are an invaluable compliment to common coagulation tests by facilitating the detection of hypercoagulable states commonly associated with orthopedic injury and postoperative status. The use of VHAs to identify hypercoagulability allows for an accurate venous thromboembolism (VTE) risk assessment and monitoring of VTE prophylaxis. Until now, the data have been insufficient to permit an individualized approach with regard to dosing and duration for VTE thromboprophylaxis. By incorporating VHAs into routine practice, orthopedic surgeons will be better equipped to diagnose and treat the complete spectrum of coagulation abnormalities faced by orthopedic patients. This work serves as an educational primer and up-to-date review of the current literature on the use of VHAs in orthopedic surgery.

Anticoagulation Monitoring in the Intensive Care Unit.

Patients with critical illness often display variable hypo- and hypercoagulable sequalae requiring intense monitoring and anticoagulation pharmacotherapy to prevent or treat inappropriate clot formation. It is imperative to understand the various stages of the clotting cascade and where each pharmacotherapy agent exerts its therapeutic effect. Common coagulation tests are utilized to monitor the areas of the clotting cascade and the effects that anticoagulant pharmacotherapy exhibits. Many novel coagulation tests are also in development. The purpose of this narrative review is to evaluate commonly utilized coagulation tests that monitor anticoagulation while in the intensive care unit.

Use of Thromboelastography and Rotational Thromboelastometry in Otolaryngology: A Narrative Review.

In the field of otolaryngology—head and neck surgery (ENT), coagulopathies present unique diagnostic and therapeutic challenges. In both hyper- and hypocoagulable patients, management of coagulopathies requires intricate attention to the nature of hemostatic competence. Common coagulation tests (CCTs) offer only a snapshot of hemostatic competence and do not provide a clear insight into the patient’s real-time hemostatic condition. Viscoelastic tests (VETs) offer a holistic and concurrent picture of the coagulation process. Although VETs have found prominent utilization in hepatic transplants, obstetrics, and emergent surgical settings, they have not been fully adopted in the realm of otolaryngology. The objective of this manuscript is to provide an overview of the literature evaluating the current utilization and possible future uses of VETs in the field of otolaryngology. The authors performed a comprehensive literature search of the utilization of VETs in otolaryngology and identified applicable studies that included descriptions of viscoelastic testing. Twenty-five studies were identified in this search, spanning topics from head and neck oncology, microvascular free flap reconstruction, obstructive sleep apnea, adenotonsillectomy, facial trauma, and epistaxis. The applicability of VETs has been demonstrated in head and neck oncology and microvascular free flap management, although their pervasiveness in practice is limited. Underutilization of VETs in the field of otolaryngology may be due to a lack of familiarity of the tests amongst practitioners. Instead, most otolaryngologists continue to rely on CCTs, including PT, PTT, INR, CBC, fibrinogen levels, and thrombin time. Learning to perform, interpret, and skillfully employ VETs in clinical and operative practice can greatly improve the management of coagulopathic patients who are at increased risk of bleeding or thrombosis.

Viscoelastic Hemostatic Assays for Postpartum Hemorrhage.

This article discusses the importance and effectiveness of viscoelastic hemostatic assays (VHAs) in assessing hemostatic competence and guiding blood component therapy (BCT) in patients with postpartum hemorrhage (PPH). In recent years, VHAs such as thromboelastography and rotational thromboelastometry have increasingly been used to guide BCT, hemostatic adjunctive therapy and prohemostatic agents in PPH. The three pillars of identifying hemostatic competence include clinical observation, common coagulation tests, and VHAs. VHAs are advantageous because they assess the cumulative contribution of all components of the blood throughout the entire formation of a clot, have fast turnaround times, and are point-of-care tests that can be followed serially. Despite these advantages, VHAs are underused due to poor understanding of correct technique and result interpretation, a paucity of widespread standardization, and a lack of large clinical trials. These VHAs can also be used in cases of uterine atony, preeclampsia, acute fatty liver of pregnancy, amniotic fluid embolism, placental abruption, genital tract trauma, surgical trauma, and inherited and prepartum acquired coagulopathies. There exists an immediate need for a point-of-care test that can equip obstetricians with rapid results on developing coagulopathic states. The use of VHAs in predicting and treating PPH, although in an incipient state, can fulfill this need.

Measuring Fibrinolysis.

Physiological fibrinolysis under normal conditions progresses slowly, in contrast to coagulation which is triggered rapidly to stop bleeding and defend against microbial invasion. Methods to detect fibrinolysis abnormalities are less simple and poorly standardized compared with common coagulation tests. Fibrinolysis can be accelerated by preparing euglobulin from plasma to reduce endogenous inhibitors, or by adding plasminogen activators to normal plasma. However, these manipulations complicate interpretation of results and diagnosis of a "fibrinolysis deficit." Many observational studies on antigen levels of fibrinolysis inhibitors, plasminogen activator inhibitor 1 or thrombin-activatable fibrinolysis inhibitor, zymogen or active enzyme have been published. However, conclusions are mixed and there are clear problems with harmonization of results. Viscoelastic methods have the advantage of being rapid and are used as point-of-care tests. They also work with whole blood, allowing the contribution of platelets to be explored. However, there are no agreed protocols for applying viscoelastic methods in acute care for the diagnosis of hyperfibrinolysis or to direct therapy. The emergence of SARS-CoV-2 and the dangers of associated coagulopathy provide new challenges. A common finding in hospitalized patients is high levels of D-dimer fibrin breakdown products, indicative of ongoing fibrinolysis. Well-established problems with D-dimer testing standardization signal that we should be cautious in using results from such tests as prognostic indicators or to target therapies.

Hemostatic Abnormalities in COVID-19: An Update.

COVID-19 has emerged as a pandemic with lung being the primarily afflicted organ. Deranged hemostasis has been observed in patients with COVID-19 with scales tipped towards a prothrombotic state. The pathogenesis differs from disseminated intravascular coagulation with a primary pulmonary localization. This is referred to as pulmonary intravascular coagulopathy with strong component of thrombo-inflammation. This is reflected in the lab tests with an increase in D-dimer which correlates with severity and outcomes of disease. Common coagulation tests such as prothrombin time, activated partial thromboplastin time are only mildly prolonged while most patients have normal to increased fibrinogen and marginal thrombocytopenia. Overall, the patients have an increase in venous and arterial thrombotic events especially in ICU patients. Routine thromboprophylaxis with low molecular weight heparin is recommended in all hospitalized patients to reduce the incidence of thrombosis. Bleeding is uncommon and treated with blood products transfusion. This review shall discuss the hemostatic abnormalities in COVID-19 patients and their impact on prognosis. In addition, strategy of thromboprophylaxis and various academic society guidelines are discussed in detail.

Use of Viscoelastography in Malignancy-Associated Coagulopathy and Thrombosis: A Review.

The relationship between malignancy and coagulopathy is one that is well documented yet incompletely understood. Clinicians have attempted to quantify the hypercoagulable state produced in various malignancies using common coagulation tests such as prothrombin time, activated partial thromboplastin time, and platelet count; however, due to these tests' focus on individual aspects of coagulation during one specific time point, they have failed to provide clinicians the complete picture of malignancy-associated coagulopathy (MAC). Viscoelastic tests (VETs), such as thromboelastography (TEG) and rotational thromboelastometry (ROTEM), are whole blood analyses that have the advantage of providing information related to the cumulative effects of plasma clotting factors, platelets, leukocytes, and red cells during all stages of the coagulation and fibrinolytic processes. VETs have gained popularity in the care of trauma patients to objectively measure trauma-induced coagulopathy (TIC), but the utility of VETs remains yet unrealized in many other medical specialties. The authors discuss the similarities and differences between TIC and MAC, and propose a mechanism for the hypercoagulable state of MAC that revolves around the thrombomodulin-thrombin complex as it switches between activating the protein C anticoagulation pathway or the thrombin activatable fibrinolysis inhibitor coagulation pathway. Additionally, they review the current literature on the use of TEG and ROTEM in patients with various malignancies. Although limited research is currently available, early results demonstrate the utility of both TEG and ROTEM in the prediction of hypercoagulable states and thromboembolic complications in oncologic patients.

Treatment tailoring for factor V deficient patients and perioperative management using global hemostatic coagulation assays

IntroductionCongenital factor V deficiency (FVD) is a rare bleeding disorder with an estimated incidence of 1 in 1000,000 in the general population. Since the common coagulation tests do not correlate with the bleeding tendency there is an unmet need to predict FVD patients' bleeding hazard prior to surgical interventions. AimTo optimize treatment prior to surgical interventions, using global coagulation assays, thrombin generation (TG) and rotating thromboelastogram (ROTEM). MethodsOur cohort included 5 patients with FVD, 4 severe and one mild. Two of them underwent TG and ROTEM prior to surgical interventions, including ex vivo spiking assays using bypass agents and platelets spiking. ResultsAll five patients exhibited prolonged PT and PTT, non-dependent on their bleeding tendency. Patient 1, who demonstrated severe bleeding phenotype, underwent surgery treated by combination of APCC (FEIBA) and platelet transfusion. Therapy was guided by global tests (TG as well as ROTEM) results. During the pre and post-operative period neither excessive bleeding nor any thrombosis was noted. In contrast, TG and ROTEM analysis of patient 4 has lead us to perform the surgery without any blood products' support. Indeed, the patient did not encounter any bleeding. ConclusionGlobal coagulation assays may be useful ancillary tools guiding treatment decisions in FVD patients undergoing surgical procedures.

Targeted Thromboelastographic (TEG) Blood Component and Pharmacologic Hemostatic Therapy in Traumatic and Acquired Coagulopathy.

Trauma-induced coagulopathy (TIC) is a recently described condition which traditionally has been diagnosed by the common coagulation tests (CCTs) such as prothrombin time/international normalized ratio (PT/INR), activated partial thromboplastin time (aPTT), platelet count, and fibrinogen levels. The varying sensitivity and specificity of these CCTs have led trauma coagulation researchers and clinicians to use Viscoelastic Tests (VET) such as Thromboelastography (TEG) to provide Targeted Thromboelastographic Hemostatic and Adjunctive Therapy (TTHAT) in a goal directed fashion to those trauma patients in need of hemostatic resuscitation. This review describes the utility of VETs, in particular, TEG, to provide TTHAT in trauma and acquired non-trauma-induced coagulopathy.

A Practical Guide to Ordering and Interpreting Coagulation Tests for Patients on Direct Oral Anticoagulants in Singapore

Direct oral anticoagulants (DOACs) are establishing themselves as principle choices for the treatment of a variety of thrombotic disorders. DOACs are also known to affect common coagulation tests which are routinely performed for patients in clinical practice. An understanding of their varied effects is crucial for the appropriate ordering of coagulation tests and their interpretation. Laboratories in public and private healthcare institutions and commercial sectors were surveyed on coagulation tests offered and their methods. A Medline and bibliography search, including a search on search engines, was performed for publications reporting the effects of dabigatran, apixaban and rivaroxaban on these coagulation tests. These papers were reviewed and summarised for consensus recommendations. Prothrombin time (PT) and activated partial thromboplastin time (aPTT) are variably affected by the DOACs and dependent of the coagulation assays used. Clinicians must know which laboratory has performed these tests to logically interpret test results. A normal PT or aPTT does not exclude the presence of residual DOACs effect. The thrombin time is sensitive to dabigatran but not apixaban or rivaroxaban. Specialised coagulation tests such as thrombophilia tests are also variably affected by the DOACs. All laboratories in Singapore however, employ similar test methods permitting a common set of recommendations for specialised coagulation testing. Knowledge of the effects of DOACs on coagulation testing is essential to determine the appropriateness of performing such tests and interpreting them coherently. Practical recommendations which are tests and location-specific are set out in this paper.

Effect of Heparin Flush in Blood Drawn from Arterial Line on Activated Clotting Time and Thromboelastogram

The usage of low dose heparin as an additive to normal saline is a very acceptable medical practice for the maintenance of arterial line. However, heparin potentially may affect the exactness of coagulation studies carried out on blood sampled from a heparin flushed arterial line. This prospective, comparative observational study was designed to evaluate the effect of blood sampling through a heparin flushed arterial catheter on the validity of common and advanced coagulation tests including activated clotting time (ACT) and thromboelastogram (TEG). Whereas heparin flush did not affect international normalized ratio (INR) and activated partial thromboplastin time (aPTT), it significantly prolonged ACT together with the R-time and K-time components of TEG. This advocated being cautious when measuring ACT and some TEG parameters from a heparin flushed arterial line in a clinical setting.

Can Unmanned Aerial Systems (Drones) Be Used for the Routine Transport of Chemistry, Hematology, and Coagulation Laboratory Specimens?

BackgroundUnmanned Aerial Systems (UAS or drones) could potentially be used for the routine transport of small goods such as diagnostic clinical laboratory specimens. To the best of our knowledge, there is no published study of the impact of UAS transportation on laboratory tests.MethodsThree paired samples were obtained from each one of 56 adult volunteers in a single phlebotomy event (336 samples total): two tubes each for chemistry, hematology, and coagulation testing respectively. 168 samples were driven to the flight field and held stationary. The other 168 samples were flown in the UAS for a range of times, from 6 to 38 minutes. After the flight, 33 of the most common chemistry, hematology, and coagulation tests were performed. Statistical methods as well as performance criteria from four distinct clinical, academic, and regulatory bodies were used to evaluate the results.ResultsResults from flown and stationary sample pairs were similar for all 33 analytes. Bias and intercepts were <10% and <13% respectively for all analytes. Bland-Altman comparisons showed a mean difference of 3.2% for Glucose and <1% for other analytes. Only bicarbonate did not meet the strictest (Royal College of Pathologists of Australasia Quality Assurance Program) performance criteria. This was due to poor precision rather than bias. There were no systematic differences between laboratory-derived (analytic) CV’s and the CV’s of our flown versus terrestrial sample pairs however CV’s from the sample pairs tended to be slightly higher than analytic CV’s. The overall concordance, based on clinical stratification (normal versus abnormal), was 97%. Length of flight had no impact on the results.ConclusionsTransportation of laboratory specimens via small UASs does not affect the accuracy of routine chemistry, hematology, and coagulation tests results from selfsame samples. However it results in slightly poorer precision for some analytes.

Reference intervals for common coagulation tests of preterm infants (CME)

Fresh-frozen plasma (FFP) is sometimes administered to nonbleeding preterm neonates who are judged to be at risk for bleeding because they have abnormal coagulation tests. The benefits/risks of this practice are not well defined. One limitation to progress is lack of reference intervals for the common coagulation tests, thus limiting precision about whether coagulation tests are indeed abnormal. In a sequential observational study, fetal blood was drawn at preterm birth (≤ 34 weeks) from the umbilical vein near the placenta. Fibrinogen, prothrombin time, activated partial thromboplastin time, D-dimer, platelet (PLT) count, and mean PLT volume were measured. Reference intervals were constructed using 5th and 95th percentile values. Associations were then sought between abnormal coagulation values at birth and bleeding problems identified during the first week. Coagulation tests were drawn at 175 preterm deliveries and the results were organized into reference intervals by gestational age. No abnormal coagulation value, either alone or in combination, predicted hemorrhage (intraventricular, gastrointestinal, or pulmonary) during the first week. However, fibrinogen exceeding the 95th percentile was associated with evidence of in utero infection/inflammation (correlations with elevated C-reactive protein, p<0.01, and elevated immature to total neutrophil ratio, p<0.001). Abnormal coagulation values at preterm birth do not predict bleeding during the first week. This suggests to us that bleeding in the days after preterm birth is not generally the result of in utero coagulopathy. These findings bring into question the value of coagulation screening of nonbleeding preterm infants and prophylactic FFP administration to those with abnormal values.

Sonoclot evaluation of whole blood coagulation in healthy adult dogs

To establish a standard protocol for analysis of canine whole blood and generate reference intervals for healthy dogs using the Sonoclot analyzer, and to compare Sonoclot values to standard and viscoelastic coagulation tests. Prospective study. Veterinary University research facility and teaching hospital. Twelve healthy random source dogs and 52 healthy dogs from the general veterinary school population. Blood sampling for viscoelastic coagulation testing. Blood was collected from 12 healthy adult dogs by jugular venipuncture. After a rest period at room temperature of 30, 60, or 120 minutes, 340 μL of citrated blood was added to 20 μL of 0.2 M CaCl(2) in 1 of 2 cuvette types warmed to 37° C. Cuvettes contained a magnetic stir-bar with glass beads (gbACT+) or only a magnetic stir-bar (nonACT). Reference interval samples were collected from 52 healthy adult dogs and analyzed in duplicate. The ACT, CR, and PF were not affected by duration of rest period for either cuvette type. ACT variability was decreased when using gbACT+ cuvettes (P < 0.05). In normal dogs reference intervals (mean ± 2 SD) using gbACT+ cuvettes were: ACT 56.0-154.0 seconds, CR 14.85-46.0, and PF 2.1-4.05. ACT correlated to TEG R-time, K-time, and angle, while CR correlated with all TEG parameters. Fibrinogen correlated with ACT, CR, and PF. Sonoclot did not correlate with other common coagulation tests. Sonoclot provides viscoelastic evaluation of canine whole blood coagulation and correlated to several TEG parameters and fibrinogen. A standard protocol and reference intervals were established.

The prevalence of abnormal results of conventional coagulation tests on admission to a trauma center

Several groups have reported that a fraction of severely injured patients have abnormal coagulation tests at presentation to trauma centers, even in the absence of significant crystalloid resuscitation. These patients have high mortality, but their prevalence in trauma populations is not clear from the reports. Records of all patients admitted to a large urban trauma center during 2000 through 2006 were searched for early measures of common coagulation tests and in-hospital mortality. Abnormal coagulation tests were increasingly frequent with increasing injury severity, ranging from 5 to 43 percent for the prothrombin time as the injury severity scores (ISSs) increased from 5 to more than 45 and 4 to 18 percent for platelet counts of less than 150 x 10(9) per L. Abnormal coagulation tests were associated with excess mortality even below conventional transfusion triggers and this was especially true for the partial thromboplastin time. Abnormal coagulation tests are common in severely injured patients. Even in the moderately injured, they are associated with higher mortality.

Rethinking the Coagulation Cascade

The concept of coagulation as a "cascade" of proteolytic reactions was a conceptual breakthrough in understanding how the coagulation process acts as a biologic amplifier. The model that it evolved into, with "extrinsic" and "intrinsic" pathways meeting in a common pathway, delineates the interactions between the coagulation proteins and provides a framework for interpreting the common screening coagulation tests. The coagulation "cascade" has significant limitations as a model of how hemostasis occurs in vivo, however. This article describes how the modern view of hemostasis has evolved to emphasize the role of cells in controlling and directing the coagulation reactions. It also highlights how host factors that are not part of the coagulation process per se can influence the effectiveness of coagulation.

Aprotinin in pediatric cardiac operations: a benefit in complex malformations and with high-dose regimen only

Background. The benefits and the current indications of aprotinin in congenital operations are not well defined. At present there are only a few studies available that have investigated a small number of patients in several heterogeneous groups of malformations. Methods. We investigated efficacy and safety of aprotinin in three groups of children <15 kg, presenting with isolated ventricular septum defect (n = 60), tetralogy of Fallot (n = 52), and transposition of the great arteries (n = 56). Low-dose aprotinin regimen A1 (500,000 KIU in pump prime only) and high-dose aprotinin A2 (50,000 KIU/kg during induction of anesthesia, 50,000 KIU/kg in pump prime, and 20,000 KIU/h continuous infusion) were compared to a control group A0 (without aprotinin) regarding perioperative blood loss, transfusion requirements, and effects on the coagulation system. Results. The most common coagulation tests of aprotinin-treated patients and the platelet numbers were comparable with those of control patients preoperatively and 15 minutes after protamine administration. A significant dose-dependent reduction in fibrin–fibrinogen split products was observed at the end of cardiopulmonary bypass in the majority of aprotinin-treated patients with transposition. In patients with ventricular septum defect and Fallot, no significant difference in blood loss and transfusion requirements could be observed between patients with or without aprotinin and no difference was observed between low- and high-dose regimen. In transposition of the great arteries, high-dose aprotinin led to significant reduction of blood loss ( p = 0.02) and postoperative blood transfusion ( p = 0.003). Severe side effects as a result of administration of aprotinin were not observed. Conclusions. High-dose aprotinin reduces blood loss and transfusion requirement only in complex congenital cardiac operations; therefore aprotinin cannot be recommended as a blood conservation agent in routine pediatric operations.

Prophylactic hemostatic drugs do not reduce hemorrhage: Thromboelastographic study during upper abdominal surgery

Although a number of hemostatic drugs are currently used during surgery to reduce hemorrhage, their effects on bleeding are still controversial. Furthermore, few studies have been made on their prophylactic effects. The purpose of this study was to clarify the effects of hemostatic drugs on bleeding. Thirty adult patients undergoing upper abdominal surgery were randomly assigned to receive carbazochrome sodium sulfonate and tranexamic acid immediately after induction of anesthesia (group H,n=15) or no hemostatic drugs (group C,n=15). Common coagulation-tests [prothrombin time (PT), activated partial thromboplastin time (APTT), fibrinogen (FIB)], thromboelastography [reaction time (R), coagulation time (K), maximum amplitude (MA), clot formation rate (α)], and determination of bleeding time were conducted before induction of anesthesia and just before the completion of surgery. PT, R, and K decreased significantly in both groups, while MA and α increased and FIB decreased significantly in group C. No significant difference in blood loss was observed between the groups. Our findings, therefore, suggest that these two hemostatic drugs do not have prophylactic effects on intraoperative bleeding. Further studies are, however, necessary before applying these results to all surgical patients.

Hemostaseological management of urological operations in patients taking aspirin using the Thrombostat 4000.

A clinical study was started in order to examine the suitability of the Thrombostat (in vitro bleeding test) (IVBT) as a diagnostic tool to prevent perioperative bleeding due to aspirin (ASA) and/or platelet function disorders of other origins. This report is based on preliminary data. Eighty three patients who had ingested ASA in the last two weeks and/or with a history of bleeding and/or documented hemorrhagic disorders requiring distinct urological operations, were included in the study. In all patients the IVBT with CaCl2, in addition to common coagulation tests, were performed. Thirteen patients stopped ASA ingestion until IVBT became normal and did not show any increased bleeding tendency. The residual patients were classified by the various operations. The following operation groups were formed: Male genitals (n = 11), inguinal/suprapubic operations (n = 7), transurethral tumor resections of the bladder (TURB) (n = 17), transurethral prostate resection (TURP) (n = 12), tumor nephrectomy (n = 8), radical prostatectomy (n = 9). Thirty six patients with a history of ASA use, but normal IVBT, served as control group (C). Thirty one patients with a history of ASA ingestion had normal in vivo bleeding times (BT) and abnormal IVBT with CaCl2 (A). Seven patients had a bleeding history and/or documented hemorrhagic disorders (B). None of the patients (A) with abnormal IVBT but normal BT displayed clinically relevant bleeding. However, the blood loss was somewhat higher compared to the controls (C), especially in patients with TURB and radical prostatectomy (not significant).(ABSTRACT TRUNCATED AT 250 WORDS)