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BACKGROUND Essential thrombocythemia (ET) is associated with increased risk of bleeding secondary to acquired von Willebrand syndrome (AVWS). Bleeding in ET requires urgent platelet reduction by cytoreductive therapy such as hydroxyurea or thrombocytapheresis. We report on the efficacy and safety of thrombocytapheresis in managing AVWS in a patient with ET and multivisceral transplantation. CASE REPORT The patient was a 51-year-old female who underwent multivisceral transplantation. Her postoperative course was complicated by bleeding from oral cavity, IV lines, gastrointestinal and upper respiratory tracts as well as vaginal bleeding, which coincided with ET flare with a platelet count of 1512 × 109 /L. Coagulation studies including von Willebrand factor (vWF) antigen and activity, vWF propeptide antigen, and vWF multimer analysis were consistent with AVWS. Hydroxyurea was initiated. However, due to major bleeding, rapidly increasing platelet count, and uncertainty of response to hydroxyurea being given through the enteral tube, thrombocytapheresis was initiated for rapid platelet reduction. The patient tolerated the procedure well. Platelet count was reduced from 1636 × 109 /L to 275 × 109 /L with rapid cessation of bleeding. The patient's condition stabilized over the next few days; however, bleeding recurred with increasing platelet count, which required a second thrombocytapheresis 8 days after the first one. The patient was maintained on hydroxyurea 500 mg twice/day. At 11-month follow-up, she had a normal platelet count and no recurrence of bleeding. DISCUSSION Thrombocytapheresis is safe and efficient in managing postoperative bleeding due to ET/AVWS in solid organ transplant patients. The procedure can be an adjunct to bridging therapy before response to hydroxyurea is achieved.

We report a case of a 56-year-old woman with a history of idiopathic thrombocytopenic purpura (ITP) following splenectomy on mycophenolate mofetil (MMF), who developed moderate bleeding after stopping MMF. Her laboratory testing suggested the presence of an abnormal circulating heparin-like anticoagulant with demonstrable anti-Xa activity. She was initially treated with antifibrinolytic therapy and was subsequently started on MMF alongside intravenous immunoglobulin, which significantly improved her bleeding symptoms. The presence of abnormal circulating heparin-like anticoagulants is a rare cause of coagulopathy. Few cases exist in the literature, with nearly all occurring in the setting of hematologic or solid-organ malignancy. The mechanism by which these endogenous anticoagulants develop is unclear. Clinical manifestations range from mild bleeding and bruising to life-threatening hemorrhage refractory to conventional therapy. Diagnosis of a heparin-like anticoagulant is based on coagulation testing as well as exclusion of other exogenous anticoagulants, acquired inhibitors, and/or factor deficiencies.

Background It is widely accepted that Point-of Care Test (PoCT) devices are useful in the detection of coagulopathies in situations of massive bleeding such as major cardiac surgery. These devices contribute to the reduction of blood transfusion. However, their implementation remains limited in Japan because of their cost and lack of health insurance support. Study design and methods Conventional coagulation tests and thromboelastography (TEG)/Sonoclot values were measured in 50 consecutive cardiac surgery cases. Clinical background information such as operative procedures was obtained from electronic medical records, and the theoretical perioperative total blood loss was calculated by measuring the hemoglobin content and total red blood cell transfusion volume. The correlation between perioperative total blood loss and the measured laboratory values or clinical parameters was evaluated by a multivariate linear regression analysis. The risk factors of the total amount of platelet transfusion and postoperative drain bleeding volume were similarly evaluated. Results No significant association between the estimated perioperative total blood loss (eTBL) and the laboratory measurements including conventional coagulation tests, TEG and Sonoclot was observed. On the other hand, postoperative drain bleeding volume was significantly associated with postoperative Sonoclot CR (p = 0.039) as well as preoperative use of oral anticoagulants and cell saver treated blood volume. Platelet transfusion amount was significantly associated with post-CBP PF and time to peak value of Sonoclot (p = 0.014 and 0.001, respectively). Conclusion Sonoclot measurements may be useful to estimate the risks of postoperative bleeding and platelet transfusion in cardiac surgeries in Japan.

Optimized acute bleeding management requires timely and reliable laboratory testing to detect and diagnose coagulopathies and guide transfusion therapy. Conventional coagulation tests (CCT) are inexpensive with minimal labor requirements, but CCTs may have delayed turnaround times. In addition, abnormal CCT values may not reflect in vivo coagulopathies that require treatment and may lead to overtransfusion. The use of viscoelastic testing (VET) has been rapidly expanding and is recommended by several recent bleeding guidelines. This review is intended to compare CCT to VET, review the strengths and weaknesses of both approaches, and evaluate and summarize the clinical studies that compared CCT-based and VET-based transfusion algorithms. Most studies of CCT vs VET transfusion algorithms favor the use of VET in the management of massively bleeding patients due to reductions in blood product utilization, bleeding, costs, and lengths of stay.

Viscoelastic hemostatic assays such as thrombelastography (TEG) and rotational thrombelastometry have proven to be important point-of-care tools in the management of acute traumatic hemorrhage. Despite the availability of prospective studies that have confirmed the utility of TEG in reducing transfusion requirements and mortality in bleeding patients when compared to conventional coagulation tests, many institutions run into barriers implementing these viscoelastic hemostatic assays due to concerns regarding cost and benefit. At our academic Level 1 trauma institution, the Division of Trauma, Critical Care, and Acute Care Surgery advocated for the addition of TEG to the clinical armamentarium of providers caring for injured patients and thus spearheaded the clinical implementation of TEG. With the approval of the central laboratory, the Division developed an extensive and well-trained team to run and interpret TEGs as well as perform machine validation and upkeep. The Division continues to perform point-of-care testing throughout the hospital today.

BACKGROUND Intraoperative plasma transfusion is common, yet little is known regarding its effects on perioperative coagulation tests or clinical outcomes. STUDY DESIGN AND METHODS This is a retrospective cohort study of adults receiving intraoperative plasma transfusion at a single center from 2011 to 2015. Relationships between plasma transfusion volume, changes in coagulation test values, and clinical outcomes, including a primary outcome of early postoperative red blood cell (RBC) transfusion, were assessed with multivariable regression analyses. Secondary outcomes included hospital mortality, intensive care unit (ICU)- and hospital-free days, intraoperative RBC transfusions, and estimated blood loss. RESULTS A total of 3393 unique patients were included, with median (IQR) transfusion of 2 (2-4) units. In multivariable analyses, higher plasma volumes were associated with worse outcomes, with each 1 mL/kg increase associated with increased odds for postoperative (1.02 [1.01-1.03], p < 0.001) and intraoperative RBCs (1.17 [1.16-1.19], p < 0.001) and fewer ICU- and hospital-free days (mean difference [95% CI], -0.08 [-0.12 to -0.05], p < 0.001; and -0.09 [-0.13 to -0.06], p < 0.001, respectively). Greater decreases in international normalized ratio (INR) following plasma transfusion were associated with decreased odds of postoperative RBCs (0.35 [0.25-0.47], p < 0.001), decreased mortality (0.50 [0.31-0.83], p = 0.007), and increased mean ICU- (1.31 [0.41-2.21], p = 0.004) and hospital-free days (1.15 [0.19-2.10], p = 0.018). CONCLUSION In patients receiving intraoperative plasma transfusion, higher transfusion volumes were associated with inferior clinical outcomes; however, greater improvements in INR were associated with improved outcomes. Future prospective studies are necessary to better define these relationships and to explore plasma transfusion triggers beyond the limitations of INR.

Background Central venous catheters are frequently inserted into patients with coagulation disorders. It is unclear whether preprocedural correction of hemostasis is beneficial. We determined the incidence of bleeding complications after central venous catheter placement in patients who had severe coagulopathy and identified potential risk factors for bleeding. Study design and methods The MEDLINE and Cochrane Library databases were systematically searched through November 2015. To be included, articles must have reported on hemorrhagic complications with specification of abnormal coagulation testing results. Severe coagulopathy was defined as a reduced platelet count of 50 × 109 /L or less, and/or an elevated international normalized ratio of 1.5 or greater, and/or a partial thromboplastin time of 45 seconds or greater. Results We included one randomized controlled trial and 21 observational studies. In total, there were 13,256 catheter insertions, including 4213 in patients with severe coagulopathy. Before 3150 central venous catheter placements, coagulopathy was not corrected. The bleeding incidence varied from 0 to 32%. The severity of coagulopathy did not predict the risk of bleeding. No study demonstrated a beneficial effect from the prophylactic administration of platelets or fresh-frozen plasma to prevent bleeding complications. Retrospective observational studies suggested that no preprocedural correction is required up to a platelet count of 20 × 109 /L and an international normalized ratio of 3.0. Conclusion The incidence of major bleeding complications after central venous catheter placement is low, even in coagulopathic patients. Based on a systematic research of the literature, strong evidence supporting the correction of hemostatic defects before central venous catheter insertion is lacking. However, well-powered randomized controlled trials will be necessary to determine the minimal platelet count, the maximal international normalized ratio, and an activated partial thromboplastin time that is safe before central venous catheter insertion.

BACKGROUND During massive hemorrhage, it is recommended to transfuse red blood cells, platelet concentrate, and fresh-frozen plasma in a ratio close to 1:1:1. To avoid the thawing process of fresh frozen plasma, lyophilized plasma (LP) is increasingly used. Evidence is limited on the activity of coagulation factors in reconstituted blood using LP and concentrated LP versions. STUDY DESIGN AND METHODS Whole blood from ten healthy volunteers was separated into red blood cell, fresh frozen plasma, and platelet concentrate units. Aliquots of red blood cells and plasma concentrate were mixed with either fresh frozen plasma (200 mL) or LP at reconstitution ratios of 2:1:1, 1:1:1, and 1:1:2. LP was used either at the recommended standard volume of 200 mL (LP200) or was more concentrated at volumes of 100 and 50 mL (LP100 and LP50, respectively). The hemostatic capacity of each reconstituted whole blood sample was tested with blood cell counts, standard coagulation tests, factor activity, thrombin generation, and viscoelastic assays. RESULTS Hematocrit, platelet counts, and fibrinogen levels of the three ratios were similar between FFP200 and LP200 units but were lower compared with the corresponding ratios in LP100 and LP50 units. The activity of procoagulant and anticoagulant factors increased linearly with the increasing plasmatic fraction and, at 1:1:2 ratio, was significantly higher in LP50 units compared with FFP200 and LP200 units. Thrombin generation was similar throughout the four plasma groups at any ratio. CONCLUSIONS Decreasing the dilution volume of LP facilitates reaching higher hematocrit and coagulation protein levels without a relevant increase in thrombin generation. This is due to preserved balance between procoagulant and anticoagulant factors in the concentrated LP preparations.

BACKGROUND Therapeutic plasma exchange (TPE) is increasingly used for treatment of antibody-mediated rejection (AMR) after solid organ transplants. There is concern that TPE may increase risk of bleeding, although data are limited. After TPE, clot-based coagulation tests may not accurately represent the levels of coagulation factors due to the effect of citrate. We investigated protein levels of fibrinogen using antigen detection method (FibAg) and correlated results with a clot-based fibrinogen activity test (Fib). STUDY DESIGN AND METHODS Nine kidney transplant recipients who received TPE for AMR were investigated. Fib, FibAg, prothrombin time/international normalized ratio (PT/INR), partial thromboplastin time (PTT), coagulation factor X chromogenic activity (CFX), and ionized calcium (iCa) were measured at pre- and post-TPE and 1, 3, 6, 9, 24, and 48 hours after the first TPE. RESULTS Mean Fib/FibAg ratio before TPE was 1.08; therefore, all Fib values were normalized (n) by dividing by 1.08. Overall, the mean normalized Fib (nFib)/FibAg ratio at post-TPE was 0.89 and returned to close to 1.0 at 6 hours after the first TPE. Decreases in nFib, FibAg, and CFX and increases in PT/INR and PTT post-TPE were observed. The lowest Fib, FibAg, CFX, platelet, and iCa levels were still at levels that would be considered sufficient for hemostasis at all time points. CONCLUSION The mean nFib/FibAg ratio after TPE was 0.89 and normalized in 6 hours, which demonstrates a persistent effect of citrate for up to 6 hours. Therefore, similar data observed in clot-based tests of PT/INR and PTT may be falsely elevated up to 6 hours after TPE due to the citrate effect.

Perioperative hemorrhage necessitating red blood cell (RBC) transfusion is an undesirable surgical complication, as RBC transfusion has consistently been associated with adverse patient outcomes.1–7 In addition, the economic toll of transfusion is increasingly well recognized, with nearly 3 million units of RBCs transfused perioperatively each year in the United States, representing more than $2.25 billion.8,9 Furthermore, hospital blood supplies are limited with more than one-quarter of US hospitals reporting surgical delays due to insufficient blood supplies and 10% of hospitals reporting at least 1 day per year where surgical blood needs cannot be met.8 It is therefore imperative in this era of increased scrutiny on health care quality that transfusion practices be uniquely tailored to clinical scenarios in which transfusion may provide evidence-based improvement in patient outcome. Preoperative platelet (PLT) counts and coagulation tests have long been used as a marker of perioperative bleeding risk; however, the value of this practice remains unclear.10 Prior studies have shown that routine preoperative coagulation tests, including PLT counts, do not reliably predict surgical bleeding complications,11–15 prompting the 2012 American Society of Anesthesiologists Task Force on Preanesthesia Evaluation to recommend against this practice unless clearly indicated by patient history and physical examination.16 However, recent evidence suggests that pre-operative thrombocytopenia is associated with significantly higher risk of blood transfusion and death in noncardiac surgery, prompting the authors to question recommendations against routine preoperative screening.17 In clinical practice, administration of PLTs in those with thrombocytopenia is frequently performed in the preoperative period in an attempt to mitigate perioperative bleeding complications including RBC requirements, surgical blood loss, and reoperation for bleeding. However, evidence to support or guide such perioperative transfusion practices is lacking.18 As such, the decision to transfuse in the perioperative period is often based on the gestalt or clinical experience of the surgeon or anesthesiologist rather than by quality evidence suggesting benefit. Moreover, PLT transfusions are associated with substantial patient risk, including a myriad of allergic, infectious, and inflammatory transfusion reactions.19,20 This investigation was designed to determine the relationship between preoperative PLT transfusion and perioperative bleeding complications in patients with thrombocytopenia undergoing noncardiac surgery in a large, tertiary care center. We hypothesized that while preoperative thrombocytopenia (i.e., PLT count ≤ 100 × 109/L) would be predictive of perioperative RBC requirements, prophylactic PLT administration would not attenuate this risk. In addition, we aimed to assess the impact of preoperative PLT transfusion on other patient-important outcomes.

Background Patients who undergo cardiopulmonary bypass (CPB) are at risk for coagulopathy. Suboptimal turnaround time (TAT) of laboratory coagulation testing results in empiric administration of blood products to treat massive bleeding. We describe our initiative in establishing the coagulation-based hemotherapy (CBH) service, a clinical pathology consultation service that uses rapid TAT coagulation testing and provides comprehensive assessment of bleeding in patients undergoing CPB. A transfusion algorithm that treats the underlying cause of coagulopathy was developed. Study Design and Methods The coagulation testing menu includes all aspects of coagulopathy with close proximity of the laboratory to the operating room to allow for rapid test results. The hemotherapy pathologist monitors laboratory results at several stages in surgery and uses a comprehensive algorithm to monitor a patient's hemostasis. The optimal number and type of blood products are selected when the patient is taken off CPB. Results The CBH service was consulted for 44 ventricular assist device implants, 30 heart transplants, and 31 other cardiovascular surgeries from May 2012 through November 2013. The TAT for laboratory tests was 15 minutes for complete blood count, antithrombin, and coagulation panel and 30 minutes for VerifyNow and thromboelastography, in comparison to 45 to 60 minutes in normal settings. The transfusion algorithms were used with optimal administration of blood components with preliminary data suggestive of reduced blood product usage and better patient outcomes. Conclusion We described the successful introduction of a novel pathology consultation service that uses a rapid TAT coagulation testing menu with transfusion algorithms for improved management of CPB patients.

Background: 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. Study Design and Methods: 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. Results: 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

Practitioners in transfusion medicine, long involved in consultations emphasizing clinical issues such as alloantibody reporting and transfusion reaction evaluation, have more recently been engaged as experts and consultants in hemostasis and coagulation. Given the growing complexity in laboratory coagulation testing and its interpretation, the shortage of specialists in this arena, and the increasing costs associated with patient management, we believe that there are vital clinical roles in hemostasis that can be readily fulfilled by transfusion medicine practitioners. The aim of this article is to briefly outline three possible models by which transfusion medicine practitioners can begin to integrate coagulation consultation into their regular clinical practice. Moreover, we discuss a novel curriculum that we are developing at our institution to more fully train transfusion medicine fellows in the fields of hemostasis and thrombosis.

Frozen plasma (FP) is commonly used in an attempt to correct coagulation defects before performing bedside, radiologically guided, or operating room procedures. Use of FP prophylactically is closely linked to results for standard coagulation tests in the laboratory, including prothrombin time, but there is a general lack of evidence supporting the predictive value of abnormalities of these tests for bleeding. Use of FP has little effect on correcting abnormal coagulation tests when mild and moderate results are recorded. There is no support for evidence of effectiveness for the prophylactic use of FP when reviewing the wider randomized controlled trial literature. When the lack of clinical effectiveness is combined with the risks of FP transfusion, such as transfusion-related acute lung injury and transfusion-associated circulatory overload, the need to challenge continued preprocedure prophylactic use of FP becomes pressing. In clinical practice, abnormalities of standard coagulation tests should not be interpreted in isolation, but alongside review of clinical bleeding history and other hemostatic markers such as platelet count. A more appropriate transfusion strategy may be one that emphasizes the therapeutic use of FP.

BACKGROUND: Rotation thromboelastometry (TEM) has been proposed as a convenient alternative to standard coagulation tests in guiding the treatment of coagulopathy during orthotopic liver transplantation (OLT). This study was aimed at assessing the value of TEM in monitoring blood coagulation and guide transfusion support in OLT. STUDY DESIGN AND METHODS: Standard coagulation and TEM (EXTEM and FIBTEM) tests were performed at four preestablished intraoperative time points in 236 OLTs and prospectively recorded in a dedicated database together with the main operative and transfusion data. Transfusion thresholds were based on standard coagulation tests. Spearman's rank correlation (ρ), linear regression, and receiver operating characteristic curves were used when appropriate. RESULTS: EXTEM maximum clot firmness (MCFEXTEM) was the TEM variable that best correlated with the platelet (PLT) and fibrinogen levels (ρ = 0.62 and ρ = 0.69, respectively). MCFFIBTEM correlated with fibrinogen level (ρ = 0.70). EXTEM clot amplitude at 10 minutes (A10EXTEM) was a good linear predictor of MCFEXTEM (R2 = 0.93). The cutoff values that best predicted the transfusion threshold for PLTs and fibrinogen were A10EXTEM = 35 mm and A10FIBTEM = 8 mm. At these values, the negative and positive predictive accuracies of TEM to predict the transfusion thresholds were 95 and 27%, respectively. CONCLUSION: A10EXTEM is an adequate TEM variable to guide therapeutic decisions during OLT. Patients with A10EXTEM of greater than 35 mm are unlikely to bleed because of coagulation deficiencies, but using A10EXTEM of not more than 35 mm as the sole transfusion criterion can lead to unnecessary utilization of PLTs and fibrinogen-rich products.

BACKGROUND: Massive transfusion (MTP) protocol design is hindered by lack of accurate assessment of coagulation. Rapid thrombelastography (r-TEG) provides point-of-care (POC) analysis of clot formation. We designed a prospective study to test the hypothesis that integrating TEG into our MTP would facilitate goal-directed therapy and provide equivalent outcomes compared to conventional coagulation testing. STUDY DESIGN AND METHODS: Thiry-four patients who received more than 6 units of red blood cells (RBCs)/6 hours who were admitted to our Level 1 trauma center after r-TEG implementation (TEG) were compared to 34 patients admitted prior to TEG implementation (Pre-TEG). Data are presented as mean ± SEM. RESULTS: Emergency department pre-TEG versus TEG shock, and coagulation indices, were not different: systolic blood pressure (94 mmHg vs.101 mmHg), temperature (35.3°C vs. 35.9°C), pH (7.16 vs. 7.11), base deficit (−13.0 vs. −14.7), lactate (6.5 vs. 8.1), international normalized ratio (INR; 1.59 vs. 1.83), and partial thromboplastin time (48.3 vs. 57.9). Although not significant, patients with Injury Severity Score range 26 to 35 were more frequent in the pre-TEG group. Fresh-frozen plasma (FFP) : RBCs, platelets : RBCs, and cryoprecipitate (cryo) : RBC ratios were not significantly different at 6 or 12 hours. INR at 6 hours did not discriminate between survivors and nonsurvivors (p = 0.10), whereas r-TEG “G” value was significantly associated with survival (p = 0.03), as was the maximum rate of thrombin generation (MRTG; mm/min) and total thrombin generation (TG; area under the curve) (p = 0.03 for both). Patients with MRTG of more than 9.2 received significantly less components of RBCs, FFP, and cryo (p = 0.048, p = 0.03, and p = 0.04, respectively). CONCLUSION: Goal-directed resuscitation via r-TEG appears useful for management of trauma-induced coagulopathy. Further experience with POC monitoring could result in more efficient management leading to a reduction of transfusion requirements.

BACKGROUND: Coagulopathy after cardiopulmonary bypass (CPB) is caused by multiple perturbations in cellular and humoral elements of coagulation. A timely and comprehensive method to evaluate hemostasis would be helpful in the management of bleeding patients after CPB. The assessment of whole blood coagulation using rotation thromboelastometry (ROTEM) was compared to coagulation tests routinely performed during cardiac surgery. STUDY DESIGN AND METHODS: Blood was obtained from 26 patients undergoing CPB surgery at baseline, at 60 minutes on CPB, at the end of CPB, and on admission to intensive care unit. ROTEM tests (extrinsically activated [EXTEM], intrinsically activated [INTEM], specific clot formation [FIBTEM]), prothrombin time, activated partial thromboplastin time, platelet (PLT) count, fibrinogen, prothrombin level, antithrombin level, and thrombin generation (TG) measurement were performed. RESULTS: We observed strong correlations between FIBTEM-amplitude at 10 minutes (A10) and fibrinogen level (r = 0.87; p

BACKGROUND: A severe intraventricular hemorrhage (IVH) in a preterm neonate can result in life-long disabilities or death. Pathogenic mechanisms responsible for IVH are incompletely understood. We postulated that if the timing of a severe IVH could be approximated by serial ultrasound, potentially relevant antecedents could be identified. STUDY DESIGN AND METHODS: We retrospectively identified all very-low-birth-weight (VLBW) neonates in our health system, over a 5-year period, with an initial head ultrasound showing no hemorrhage but a subsequent ultrasound showing a Grade 3 or 4. Controls that did not develop an IVH were matched with cases using demographic features and degree of illness measures. RESULTS: Fifty-four cases were matched (1:2) with controls. No differences were found between cases and controls in initial pH, sepsis, ventilation, coagulation studies, or proportion with severe thrombocytopenia. However, during the period when the head ultrasound was normal, cases were more likely to have had a red blood cell (RBC) transfusion (p

BACKGROUND: Despite the improvement in the assistance and treatment of preterm infants, intraventricular hemorrhage (IVH) remains a frequent complication in these patients. Our aim was to demonstrate the hypothesis that a coagulopathy screening and the early treatment with fresh-frozen plasma (FFP) of proven coagulopathy may contribute to decrease the occurrence of IVH in infants with gestational age of less than 29 weeks. STUDY DESIGN AND METHODS: This study compared two cohorts of infants who received FFP (10 mL/kg) after the evidence of pathologic coagulation tests performed within 2 hours after birth (screening group, n = 127) or after the development of bleedings and evidence of pathologic coagulation tests (no-screening group, n = 91). RESULTS: The screening strategy decreased the relative risk (RR) of developing IVH (RR = 0.65; 95% confidence interval, 0.44-0.98) compared to no-screening strategy, but the effect was limited to infants born at 23 to 26 weeks of gestation in whom screening strategy lowered IVH occurrence (34.5% vs. 61.1%, p = 0.008). CONCLUSIONS: A coagulopathy screening strategy decreases the risk of developing IVH in preterm infants but this effect is limited to infants born at 23 to 26 weeks of gestation.

BACKGROUND: 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. STUDY DESIGN AND METHODS: 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. RESULTS: 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 × 109 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. CONCLUSIONS: Abnormal coagulation tests are common in severely injured patients. Even in the moderately injured, they are associated with higher mortality.

BACKGROUND: Hydroxyethyl starch (HES) solutions are readily available colloids, but their widespread use is shadowed by controversies surrounding their effects on bleeding. This retrospective study was conducted to evaluate the relationship between Hextend (HEX; Hospira, Inc.) doses of 1 to 20 mL/kg and allogeneic transfusion and 24-hour chest tube drainage (CTD) in cardiac surgeries at a blood conservation center. STUDY DESIGN AND METHODS: After institutional review board approval, data on 748 patients undergoing coronary artery bypass grafting (CABG), valve, or combined CABG and valve surgeries were collected. Cases not receiving HEX (due to contraindications, e.g., renal failure, bleeding diathesis) or receiving more than 20 mL per kg HEX, not accepting transfusions, or requiring more extensive surgery were excluded, and the remaining 621 cases were analyzed. RESULTS: Overall transfusion rate and mean CTD were 12.7 percent and 460.4 mL, respectively. Patients who received transfusions received more HEX (10.8 mL/kg vs. 9.8 mL/kg; p = 0.043) but HEX per kg was not associated with higher transfusion rates in multivariate analysis (p = 0.077). HEX per kg was associated with CTD in both uni- and multivariate analyzes (p

Item does not contain fulltext BACKGROUND: Bleeding upon major surgery or severe trauma is treated by transfusion with crystalloids, colloids, or plasma. This treatment, however, can lead to dilutional coagulopathy and impaired hemostasis. We investigated the suitability of two integrative coagulation tests to measure the hemostatic activity of diluted plasma. STUDY DESIGN AND METHODS: Plasma from healthy donors was diluted in vitro with saline or colloid (venofundin or gelofusin). Coagulant activity in response to tissue factor was monitored by calibrated automated thrombin (CAT) generation and rotational thromboelastography (TEG), detecting formation of elastic fibrin clots. Plasma from patients receiving fluid infusion during coronary artery bypass grafting (CABG) was analyzed with the same assays. RESULTS: Optimal activity of CAT and TEG assays required the presence of 10 pmol per L tissue factor and 4 micromol per L phospholipid vesicles or 100 x 10(9) platelets (PLTs) per L. Strikingly, thrombin generation and clot formation became impaired at a higher extent of dilution with PLTs present (< or =40% plasma) than with phospholipid vesicles present (< or =60% plasma). Colloids aggravated the dilution effect on clot formation, but FFP antagonized the dilution effect on thrombin and clot formation. In contrast, fibrinogen and Factor (F)XIII only restored the impaired clot formation. In plasma samples from patients undergoing CABG, CAT and TEG assay variables were altered to an extent corresponding with the volume of fluid infusion. CONCLUSION: Thrombin generation and clot formation are reduced at a plasma dilution of more than 40 percent. In either process, PLTs can partly compensate for the dilution effect. In vitro dilution with colloids impaired fibrin clot elasticity compared to saline.

Background Solvent/detergent (S/D) inactivates enveloped viruses in plasma. The current technology requires a plasma fractionation facility and is applied to large plasma pools, which increases the cost and risks of exposure to S/D-resistant pathogens and lowers the content of protein S and alpha2-antiplasmin. Two S/D treatment procedures for single donations or minipools of plasma have been developed with a single-use bag system. Study design and methods Frozen plasma samples were thawed and treated in disposable bags with either 2 percent tri(n-butyl)phosphate (TnBP) at 37 degrees C or 1 percent TnBP and 1 percent Triton X-45 at 31 degrees C for 4 hours. Plasma samples were extracted three times with 7.5 percent sterile castor oil to remove TnBP and Triton X-45. The TnBP-treated plasma samples were further subjected to a clarifying centrifugation (3800 x g, 30 min). Final plasma samples were dispensed into individual bags and frozen at -30 degrees C. Plasma quality was assessed at each step of the procedures. Results Both processes yielded greater than 90 percent mean recovery of coagulation factors (clottable fibrinogen, von Willebrand factor, and factors VIII, V, VII, IX, X, and XI), anticoagulants (protein C, protein S), protease inhibitors (antithrombin, alpha2-antiplasmin), total protein, albumin, and immunoglobulins. Global coagulation tests of the treated plasma samples were normal. Final TnBP and Triton X-45 content was less than 10 and 50 ppm, respectively. Conclusion S/D treatment of plasma can be performed in a closed-bag system under conditions that maintain plasma protein quality. The technology is simple, presents advantages over the industrial large-scale S/D plasma process, and could be performed in blood centers.

BACKGROUND : An Arg 60 -to-Leu mutation was found in the first cytoplasmic loop of the PLT TxA 2 receptor as a new congenital PLT disorder characterized by impaired responsiveness to TxA 2 . However, it has not been clarified whether DDAVP is effective in correcting the bleeding time (BT) in this PLT disorder. STUDY DESIGN AND METHODS : DDAVP (0.4 μg/kg) was intravenously administered over 20 minutes in five patients with this PLT disorder, and template BT, PLT retention to glass beads, PLT aggregation, and a coagulation study were performed before and after the infusion of DDAVP. PLT TxA 2 synthesis defects (cyclo-oxygenase deficiency, volunteers taking aspirin), thrombasthenia, and Bernard–Soulier syndrome were also included in this study. RESULTS : The normalization of BT was found in all patients with this PLT disorder, and one of the patients successfully underwent oral surgical procedures with DDAVP as the only hemostatic agent. DDAVP was also efficacious in the TxA 2 synthesis defect but not in other disorders. FVIII coagulation activity, vWF antigen, and ristocetin cofactor significantly increased in all patients after DDAVP, but no changes were seen in the PLT retention rate and PLT aggregation study after DDAVP infusion. CONCLUSION : DDAVP was effective in correcting BT in patients with impaired responsiveness to TxA 2 as well as impaired production of TxA 2.

BACKGROUND : Component therapy has become the accepted standard of care in transfusion medicine. In instances of large blood loss, the transfusion of whole blood rather than the combination of RBCs and FFP is rational and may be preferred. STUDY DESIGN AND METHODS : In a controlled, prospective, randomized study of 33 patients undergoing orthotopic liver transplantation, the effectiveness of component therapy (RBCs and FFP) was compared with the use of whole blood. Coagulation tests (prothrombin time and activated partial thromboplastin time), clotting factor levels (FV, FVIII, fibrinogen), platelet counts, the number of donor exposures, and the total volume of blood transfused for the whole-blood group and the component-therapy group were compared at designated times before surgery, during surgery, and 24 hours after surgery. RESULTS : There was a significant difference (p = 0.015) in the median number of donor exposures for RBCs and FFP, with fewer occuring in the whole-blood group (n = 14.5) compared with the component group (n = 25). There was no significant difference between groups in coagulation profiles during any of the phases of surgery except for a mild decrease in fibrinogen levels in the whole-blood group at the conclusion of surgery. There were no differences between the groups in the median volume of blood component replacement, the median age of blood components, the patients' Hct or the number of RBC-containing components transfused. CONCLUSION : Whole blood, when compared with component therapy, is associated with fewer donor exposures yet provided equally effective replacement therapy for blood loss in liver transplantation patients.

The effects of hydroxyethyl starch (HES) on hemostasis were investigated extensively. In order to simulate acute blood loss due to surgery or trauma, one unit (450 ml) of blood was drawn from normal healthy men. This was followed by a 1-liter infusion over 60 minutes of either 6 percent HES, 5 percent albumin, or 0.9 percent sodium chloride (NaCl) as replacement. Coagulation studies were performed before phlebotomy, before infusion and at 0, 4, 20, 27, and 92 hours following infusion. Following infusion of HES and albumin, plasma fibrinogen and antithrombin-III levels fell slightly due to plasma volume expansion and hemodilution. In subjects receiving HES, partial thromboplastin times (PTTs) were significantly (p less than .05) prolonged and factor VIII activities were significantly (p less than .05) decreased when compared to the albumin and NaCl groups. These findings could not be attributed solely to hemodilution. The effects of HES on PTT and factor VIII could not be correlated with plasma HES levels; neither could they be reproduced in vitro by mixing HES with normal plasma. Mean values of the following studies remained normal after infusion of all replacement fluids: prothrombin time, bleeding time, fibrin monomer, fibrin- fibrinogen degradation products, platelet adhesion, circulating platelet aggregates, and platelet count.(ABSTRACT TRUNCATED AT 250 WORDS)

A three-part study to determine the reasons for fresh-frozen plasma (FFP) transfusions at hospitals in southeastern Wisconsin was conducted. During a 1-month period, hospital transfusion services reported that patients undergoing open-heart surgery received 42 percent, medical patients 26 percent, noncardiac surgery patients 23 percent, neonatal patients 1 percent, and other patients 7 percent of the FFP transfused. In the second phase of the study, the records of 102 patients receiving FFP during a 1-month period at two teaching hospitals were reviewed. Justification for the FFP transfusion was provided in the hospital chart for only 11 percent of the transfusion episodes, although abnormal results of coagulation studies or signs of hypovolemia were recorded for an additional 51 percent. Frequently, FFP and red cell (RBC) transfusions were given during the same transfusion episode. In the third phase of the study, clinicians completed a questionnaire specifying their "trigger" for prescribing FFP: bleeding (43% of episodes), abnormal coagulation studies (26%), signs/symptoms of hypovolemia (16%), and "other" (15%). They judged that the FFP transfusion was effective in 47 percent of transfusion episodes and ineffective in only 6 percent. These findings indicate that FFP is used mainly as a source of coagulation factor replacement in hospitals served by The Blood Center of Southeastern Wisconsin, that justification for FFP use rarely is provided in patient records, that both FFP and RBCs are frequently transfused together, and that clinicians believe FFP is beneficial for their patients. Educational efforts addressing appropriate use of FFP should be initiated.

This-study evaluates the effects of the transfusion of frozen-thawed blood protected by hydroxyethyl starch (HES) on shocked monkeys. Particular attention is directed toward the study of coagulation in view of previous reports of coagulopathies caused by hydroxyethyl atarch. In vivo studies were done in 13 shocked monkey that received either homologous or autologous blood which had been from and thawed with 14 per cent HES aa the cryoprotective agent. Multiple coagulation studies were obtained on the monkeys, and histopathological evaluations were performed. There wa8 no evidence of increased bleeding or bleeding tendencies in the monkeys transfused with HES preserved blood. Serum chemistry values were not significantly altered in animals that received blood pre SCN~ by HES nor in those that received large quantities of HES alone. Histopathological examination of biopsy and autopsy material demonstrated no changes which could be related to hydmxyethyl starch. CRYOPROTECTIVE agents used in freeze preservation of whole blood can be divided into two major groups: those that protect by intracellular mechanisms and those that are primarily extracellular in action.18 The intracellular agents, glycerol been shown to produce a satisfactory degree of cryoprotection. These substances must be thoroughly removed postthaw by washing. Hydroxyethyl starch (HES) is a plasma expander similar to Dextran and PVP1.

With the growth in autologous blood programs and the increased scrutiny of the indications for transfusion of fresh-frozen plasma (FFP), an increase has been seen in the number of occasions on which FFP was requested and thawed but then not transfused. The coagulation properties of FFP units that were refrozen and then rethawed were therefore studied. Fifty-eight units of plasma were studied, with each experimental unit of FFP paired with an identical control unit. Experimental units were frozen, stored at -65 degrees C, thawed, stored at 1 to 6 degrees C for various periods of time up to 24 hours, and then refrozen, stored at -65 degrees C, rethawed, and stored again in the refrigerator for up to 24 hours. Control units were frozen once at the time the experimental units were first frozen and thawed once at the time of the second thaw of the experimental units. Aliquots of plasma were sampled periodically and were later batch-tested for prothrombin time (PT), activated partial thromboplastin time (aPTT), and factor V and VIII:C activity. The results of coagulation testing of the twice-frozen plasmas were always within the normal range. There was a slight but statistically valid prolongation of the PT and aPTT and a decrease in the factor V and VIII:C levels for twice-frozen plasma compared with control plasma. The greatest decline occurred in the level of factor VIII:C. The measured deterioration in coagulation of twice-frozen FFP is unlikely to be of clinical importance. Refreezing FFP may eventually prove useful for rare donor, autologous, and massive transfusion programs.

Extensive coagulation studies have been carried out on patients undergoing cardiac surgery for whom the blood for extracorporeal circulation was drawn in acid-citrate-dextrose solution 24 to 48 hours before surgery, buffered with tris (hydroxymethyl) aminomethane (THAM) just prior to perfusion and diluted with low molecular weight dextran or 2.5% dextrose and 0.45% saline. Similar studies were carried out on patients given fresh whole heparinized blood. The results have shown no changes in coagulation parameters other than those expected from the use of blood stored for short periods of time. These changes are minimal reduction of platelet count and Factor V levels. The results are confirmed by postperfusion studies on an additional 60 patients (35 ACD, 25 heparin) who have required protamine titration after perfusion. The use of blood buffered with THAM has no adverse effects on the hemostasis of patients perfused with this medium.

Recent investigation has shown that the addition of adenine to citrated blood significantly prolongs the useful shelf life of banked blood. The present study was undertaken to ascertain if adenine-ACD solutions were toxic to humans. Seven healthy adult male volunteers were infused with 0.5-liter and 1.0-liter quantities of the ACD-ade-nine solution used to preserve and anticoagulate blood. The rates of infusion were comparable to those required for the resuscitation of seriously wounded wartime casualties. The larger dose caused mild circumoral paresthesia in all subjects and slight electrocardiographic prolongation of the QT interval in two volunteers. Other clinical and laboratory studies showed no changes that could be attributed to either adenine or citrate toxicity. The unchanged coagulation tests in our subjects suggested that the abnormalities observed after massive blood transfusion are probably unrelated to the infusion of citrate.

The literature related to the effects of hydroxyethyl starch on blood coagulation was reviewed to determine whether or not recipients are placed at risk of hemorrhage or thrombosis. Effects on coagulation observed when blood and HES were mixed in vitro were trivial and seemed related simply to dilution. HES affected coagulation in vivo in a dose- related fashion. When infused in moderate amounts (as employed in leukapheresis), HES rarely, if ever, caused overt bleeding, and only minor changes of laboratory coagulation tests were detected. Following massive infusions, however, a wide variety of laboratory abnormalities were observed, and hemorrhage was documented in some reports. It must be emphasized that information is limited. Not all investigators employed a complete battery of modern techniques; data regarding massive infusions are derived almost exclusively from animal studies; and data are insufficient to determine the effects of HES on thrombosis. Additional studies are required to completely define the relationship between HES and coagulation in man.

The present study defines excessive bleeding in patients who undergo cardiopulmonary bypass, and evaluates the use of coagulation testing to predict those patients that bleed excessively. Evaluation of 774 consecutive patients undergoing aortocoronary bypass surgery was carried out. Cardiopulmonary bypass consisted of a bloodless prime and a Harvey bubble oxygenator. In the postoperative period, excessive hemorrhage was defined as that exceeding 600 ml chest tube drainage in the first eight hours. One hundred and sixty-three patients (21%) were noted to be in this category. Excessive bleeding postoperatively was best predicted by a PTT greater than 45 seconds, a PT greater than 19 seconds, a fibrinogen level less than 225 mg/dl and a TFT equal to or less than 1:32. These laboratory findings occur singly or in combination. The assessment of platelet, numbers or function and fibrin(ogen) split products were of no prognostic value. Using these criteria, the re-exploration rate for excessive hemorrhage and/or tamponade was 0.6 per cent (5 out of 774 patients). No preoperative laboratory test of hemostatic function was useful in predicting coagulopathies resulting from cardiopulmonary bypass.

Coagulation studies were serially performed before and after repeated plasma exchange in seven patients with myashtenia gravis. The fall in platelets and coagulation factor activities after plasmapheresis using a replacement material devoid of clotting factors was not so low that bleeding episodes were to be feared and no hemorrhages were observed. In contrast, thrombotic phenomena were suspected in two patients. Antithrombin III fell to undetectable levels in some cases. This finding associated with elevated values of factor VIII related antigen, factor VIII coagulant activity and von Willebrand factor suggested a potential danger of thrombosis in such treated patients.