Publications by authors named "Shiu-Ki Hui"

28 Publications

  • Page 1 of 1

Trimester-specific thromboelastic values and coagulation activation markers in pregnancy compared across trimesters and compared to the nonpregnant state.

Int J Lab Hematol 2021 Jan 25. Epub 2021 Jan 25.

The Department of Medicine, Texas Children's Hospital and Baylor College of Medicine, Houston, TX, USA.

Introduction: Rotational thromboelastometry (ROTEM) rapidly identifies deficits underlying coagulopathy during massive hemorrhage. Prompt coagulopathy correction is balanced with the risk of blood product overutilization, making the ability to quickly target therapy highly desirable. However, data about ROTEM reference ranges in pregnancy are limited. We hypothesized that ROTEM parameters change across trimesters of pregnancy and differ from the nonpregnant state. Also, we sought to identify which hemostatic test best predicts coagulation activation during pregnancy.

Methods: A prospective cohort study in healthy pregnant patients in the first (n = 34), second (n = 34), and third trimesters (n = 41) against healthy, nonpregnant controls (n = 33) was performed. Citrated blood was collected, and ROTEM, complete blood count, and plasma-based assays of coagulation were performed. Mean ± SD or median [IQR] were compared across trimesters and between each trimester against the nonpregnant state. ROTEM parameters vs. plasma-based assays were also compared.

Results: Maximum clot firmness and A10 in FIBTEM correlated strongly with fibrinogen level. INTEM and EXTEM values demonstrated only weak to modest correlation with corresponding tests using plasma assays. Thrombin antithrombin complex (TAT) increased from the first trimester onward, whereas other coagulation activation markers did not show difference compared with control group.

Conclusion: Rotational thromboelastometry parameters differ variably across trimesters of pregnancy and compared with the nonpregnant state. The development and use of pregnancy-specific values are critical to the proper clinical interpretation of ROTEM in women with serious hemorrhage during different stages in pregnancy. TAT was the earliest laboratory marker for coagulation activation among others.
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http://dx.doi.org/10.1111/ijlh.13472DOI Listing
January 2021

Evaluation and Management of Coagulopathies and Thrombophilias in Pediatric Patients.

Clin Lab Med 2021 Mar 15;41(1):83-100. Epub 2020 Dec 15.

Pathology & Immunology, Baylor College of Medicine, 6621 Fannin Street, Houston, TX 77030, USA. Electronic address:

The diagnosis of coagulopathy or thrombophilia in pediatric patients can be challenging. Congenital coagulopathies often present in the pediatric period and require appropriate work-up for diagnosis and ongoing management. Acquired coagulopathies of childhood are frequently encountered in hospitalized children and warrant appropriate coagulation testing for goal-directed therapy. The incidence of thrombosis is increasing in pediatric patients. After identifying the presence of thrombus, acute management includes initiating therapeutic anticoagulation. Choice of anticoagulant depends on patient's clinical status, along with availability of the anticoagulant. Thrombophilia evaluation is performed when children present with spontaneous thrombosis. Thrombophilia tests are inaccurate during acute illness.
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http://dx.doi.org/10.1016/j.cll.2020.10.006DOI Listing
March 2021

Low antithrombin levels in neonates and infants undergoing congenital heart surgery result in more red blood cell and plasma transfusion on cardiopulmonary bypass.

Transfusion 2020 Dec 17;60(12):2841-2848. Epub 2020 Sep 17.

Department of Pathology, Texas Children's Hospital, Houston, Texas, USA.

Background: Neonates have lower levels of antithrombin (AT) due to immature liver synthetic function. AT deficiency may lead to inadequate anticoagulation with heparin during cardiac surgery resulting in consumption of coagulation factors and increased blood transfusion. The goal of this study is to examine the effect of AT level on the transfusion requirements of neonates and infants undergoing open heart surgery.

Study Design And Methods: This is a prospective, observational study at a tertiary pediatric referral center. Neonates and infants up to 6 months of age undergoing congenital heart surgery with cardiopulmonary bypass (CPB) were enrolled. Demographic, intraoperative, transfusion, and complications data were collected. Preoperative AT level was measured after induction of anesthesia. Prior to separation from CPB, a second blood sample was drawn and AT, thrombin antithrombin complex (TAT), D-dimer, and anti-Xa levels were measured. Linear and logistic regression were performed for data analysis.

Results: Preoperative low AT level was significantly associated with increased transfusion of red blood cells (RBCs) and fresh frozen plasma (FFP) during CPB, but not after separation from CPB. The incidence of thrombosis and re-operation were not associated with preoperative AT levels. There was no association between TAT, D-dimer, and anti-Xa levels at the end of CPB and preoperative AT levels.

Conclusion: Low preoperative AT level is associated with increased transfusion of RBC and FFP on CPB in neonates and infants undergoing congenital heart surgery. Low preoperative AT level did not result in coagulation activation after CPB and after surgery.
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http://dx.doi.org/10.1111/trf.16082DOI Listing
December 2020

C-reactive protein-induced activated partial thromboplastin time prolongation in heparinized samples is attenuated by elevated factor VIII.

Int J Lab Hematol 2021 Feb 19;43(1):139-142. Epub 2020 Aug 19.

Departments of Pathology & Immunology, Texas Children's Hospital, Baylor College of Medicine, Houston, TX, USA.

Introduction: Activated partial thromboplastin time (aPTT) and antifactor Xa (anti-Xa) activity are used to monitor unfractionated heparin therapy in children on extracorporeal membrane oxygenation (ECMO). Elevated C-reactive protein (CRP) can prolong aPTT and cause discrepancy between these two assays. We aimed to evaluate CRP effect on aPTT and anti-Xa assays in the presence of heparin and to determine whether elevated CRP affects laboratory monitoring in pediatric ECMO patients.

Materials And Methods: Citrated normal specimens were spiked with CRP, heparin, and recombinant factor VIII (FVIII) and followed by measurement of aPTT and anti-Xa activity. Additionally, aPTT, anti-Xa activity, FVIII, fibrinogen, and CRP were measured in 18 ECMO specimens.

Results: Elevated CRP prolonged aPTT in normal specimens with or without heparin, but did not affect anti-Xa assay. In contrast, ECMO specimens showed similar aPTT and anti-Xa values regardless of CRP level. Elevated CRP in specimens was accompanied by increased fibrinogen and FVIII activity. Additional in vitro experiments confirmed that FVIII spiked simultaneously with CRP attenuated CRP-induced aPTT prolongation in heparinized specimens.

Conclusion: In vitro CRP-induced aPTT prolongation is not observed in pediatric ECMO samples due to concomitant FVIII increase. Discordant changes of CRP and FVIII in plasma could contribute to aPTT/anti-Xa discrepancies observed during heparin therapy in the pediatric population. The anti-Xa assay is preferable for heparin monitoring in pediatric ECMO settings.
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http://dx.doi.org/10.1111/ijlh.13314DOI Listing
February 2021

Structural characterization of a clinically described heparin-like substance in plasma causing bleeding.

Carbohydr Polym 2020 Sep 19;244:116443. Epub 2020 May 19.

Department of Chemistry and Chemical Biology, Center for Biotechnology and Interdisciplinary Studies, Rensselaer Polytechnic Institute, Troy, NY, 12180, USA; Department of Chemical and Biological Engineering, Rensselaer Polytechnic Institute, Troy, NY, 12180, USA; Department of Biology, Rensselaer Polytechnic Institute, Troy, NY, 12180, USA; Department of Biomedical Engineering, Rensselaer Polytechnic Institute, Troy, NY, 12180, USA. Electronic address:

Heparin-like substances (HLS) have been described in various clinical situations, including in settings of liver disease associated with infection, transplant, and metastasis. HLS are generally attributed to circulating glycosaminoglycans. Initial results for this patient showed coagulopathy due to liver disease without HLS. Two weeks after liver transplantation, a 10 year-old female with liver failure patient began to bleed from catheter insertion sites, mouth, and nares and HLS was suspected. The patient subsequently died and these clinical samples resulted in the isolation of a single heparan sulfate (HS) present at high concentrations in the plasma. Analysis of this HS showed it had an intermediate between heparin and HS with low antithrombin-mediated anticoagulant activity. We speculate that this 10-year old patient might have a platelet function defect influenced by this unusual HS. Endothelial defects not measurable by our methods might have also contributed to the observed bleeding complications.
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http://dx.doi.org/10.1016/j.carbpol.2020.116443DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7337982PMC
September 2020

Tortuosity-powered microfluidic device for assessment of thrombosis and antithrombotic therapy in whole blood.

Sci Rep 2020 04 1;10(1):5742. Epub 2020 Apr 1.

Department of Biomedical Engineering, Texas A&M College of Engineering, College Station, TX, USA.

Accurate assessment of blood thrombosis and antithrombotic therapy is essential for the management of patients in a variety of clinical conditions, including surgery and on extracorporeal life support. However, current monitoring devices do not measure the effects of hemodynamic forces that contribute significantly to coagulation, platelet function and fibrin formation. This limits the extent to which current assays can predict clotting status in patients. Here, we demonstrate that a biomimetic microfluidic device consisting stenosed and tortuous arteriolar vessels would analyze blood clotting under flow, while requiring a small blood volume. When the device is connected to an inline pressure sensor a clotting time analysis is applied, allowing for the accurate measurement of coagulation, platelets and fibrin content. Furthermore, this device detects a prolonged clotting time in clinical blood samples drawn from pediatric patients on extracorporeal membrane oxygenation receiving anticoagulant therapy. Thus, this tortuosity activated microfluidic device could lead to a more quantitative and rapid assessment of clotting disorders and their treatment.
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http://dx.doi.org/10.1038/s41598-020-62768-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7113244PMC
April 2020

Monitoring bivalirudin therapy in children on extracorporeal circulatory support devices: Thromboelastometry versus routine coagulation testing.

Thromb Res 2020 02 12;186:54-57. Epub 2019 Dec 12.

Department of Pathology & Immunology, Texas Children's Hospital, Baylor College of Medicine, Houston, TX, United States of America.

Introduction: Bivalirudin is an alternative to heparin anticoagulation in infants and children in the setting of extracorporeal life support (ECLS). While activated partial thromboplastin time (aPTT) is widely accepted as the standard test to monitor bivalirudin therapy, the usefulness of thromboelastometry (ROTEM) to monitor bivalirudin infusion in the setting of ECLS is unknown.

Objective: We aimed to assess the utility of ROTEM in monitoring hemostasis and bivalirudin effect in children on either extracorporeal membrane oxygenation (ECMO) or ventricular assist devices (VAD) compared to standard plasma based coagulation assays.

Methods: A retrospective study of children undergoing bivalirudin infusion for ECMO/VAD support from a tertiary care pediatric hospital (January 2017-June 2018) was performed. ROTEM assays for extrinsic (EXTEM) and intrinsic (INTEM) coagulation pathways, INTEM with heparinase (HEPTEM), fibrin formation (FIBTEM) with measurement of the clotting time (CT) and maximum clot firmness (MCF) were compared to routine hemostasis testing including: aPTT, aPTT Hepzyme (HPTT), prothrombin time (PT), fibrinogen and platelet count.

Results: One hundred and six blood samples from 18 children were tested. There was a strong positive correlation between HPTT and HEPTEM CT, and moderate correlation between aPTT and INTEM CT. The bivalirudin dose did not correlate with any test, but displayed strong age-dependence, with infants requiring higher doses of bivalirudin to maintain therapeutic targets. Excellent correlation was found between FIBTEM MCF values and fibrinogen, but FIBTEM overestimated fibrinogen level when platelet count was >300 × 10/L. Heparin-like effect was identified in 39% of specimens, and an improved correlation between aPTT and INTEM CT was observed in specimens without heparinoids.

Conclusions: In the setting of bivalirudin therapy, prolongation of CT on INTEM and HEPTEM showed moderate to strong correlation with aPTT and HPTT, and therefore, may provide a good alternative to these assays. In addition, HPTT and HEPTEM CT might be preferable for monitoring bivalirudin in the setting of ECLS due to frequent detection of heparin-like effect.
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http://dx.doi.org/10.1016/j.thromres.2019.12.007DOI Listing
February 2020

Hemostatic Management of Extracorporeal Circuits Including Cardiopulmonary Bypass and Extracorporeal Membrane Oxygenation.

Semin Thromb Hemost 2020 Feb 13;46(1):62-72. Epub 2019 Dec 13.

Department of Pathology & Immunology, Baylor College of Medicine, Houston, Texas.

Cardiopulmonary bypass and extracorporeal membrane oxygenation (ECMO) cause hemostatic derangements that can predispose patients to both bleeding and thrombotic complications. Often, patients present for urgent surgery while taking medications including antiplatelet agents, vitamin K antagonists, and direct oral anticoagulants, which must be recognized, monitored, and managed. During extracorporeal circulation, appropriate anticoagulation, most commonly with heparin, is required to maintain blood flow and avoid thrombotic complications. However, anticoagulation and other effects of extracorporeal circuits can also have an undesired consequence of bleeding. Extracorporeal circulation leads to coagulopathy that may require therapy with blood products such as platelets, cryoprecipitate, and plasma in case a patient bleeds. Platelet dysfunction related to exposure to a foreign circuit is a primary concern, as is the development of acquired von Willebrand syndrome, which frequently remains undetected on routine testing. Hemorrhagic complications in ECMO, such as intracranial hemorrhage, pulmonary hemorrhage, and hemithorax, can occur. Hemostatic agents including antifibrinolytics, desmopressin, fibrinogen concentrates, and other factor concentrates may be needed to achieve hemostasis in these often-challenging patients. Managing bleeding on extracorporeal support requires careful monitoring and a thoughtful approach.
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http://dx.doi.org/10.1055/s-0039-3400273DOI Listing
February 2020

Severe hypocalcemia during surgery for placenta accreta spectrum: The case for empiric replacement.

Acta Obstet Gynecol Scand 2019 10 23;98(10):1326-1331. Epub 2019 May 23.

Department of Obstetrics and Gynecology, Baylor College of Medicine and Texas Children's Hospital, Houston, TX, USA.

Introduction: We aimed to determine predictive factors for severe hypocalcemia in women with placenta accreta spectrum.

Material And Methods: Study of 123 women with histology-proven placenta accreta spectrum with cesarean hysterectomy between 2011 and 2017. Two groups were selected: Cases: critically low ("panic value") serum total calcium (≤7 mg/dL) and Controls: normal serum total calcium (≥8.5 mg/dL). Regression and receiver operating characteristic (ROC) analyses were performed to evaluate the potential associations.

Results: There were 13 women with critically low (cases) and 18 with normal calcium (controls). Baseline characteristics were not statistically different. The median estimated blood loss, units of red blood cells (RBCs) transfused and volume of crystalloid transfused, were higher in the low calcium group. Six out of 13 (46.2%) cases had received ≥4 units of RBCs during surgery vs 2 of 18 (11.1%) controls (P = 0.04). ROC analysis showed that estimated blood loss, units of RBCs transfused, and crystalloid transfused were associated with severe hypocalcemia and univariate regression analysis confirmed that estimated blood loss ≥1500 mL, RBC transfusion ≥4 units, and crystalloid transfused ≥4L were associated with severe hypocalcemia.

Conclusions: Intraoperative transfusion of ≥4 units RBCs is predictive of the development of severe hypocalcemia in placenta accreta spectrum patients experiencing active bleeding. Empiric replacement of 1 g CaCL is recommended for every 4 U RBC transfused.
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http://dx.doi.org/10.1111/aogs.13636DOI Listing
October 2019

Coagulopathy in surgical management of placenta accreta spectrum.

Eur J Obstet Gynecol Reprod Biol 2019 Jun 19;237:126-130. Epub 2019 Apr 19.

Division of Maternal Fetal Medicine, Department of Obstetrics and Gynecology, Baylor College of Medicine and Texas Children's Hospital, Houston, TX, United States.

Background: One of the major complications of the placenta accreta spectrum (PAS) is the development of coagulopathy. The detection, prevention and prompt treatment of coagulopathy may be lifesaving.

Objective: Our objective was to study selected factors associated with coagulopathy in the management of PAS by a well-established multidisciplinary team.

Study Design: This is a retrospective review of all patients with pathologically proven PAS (including placenta accreta, increta or percreta) who underwent surgery by our multidisciplinary team between January 2011 and February 2017. Coagulopathy in this setting was defined as a platelet count of <100,000/mm, international normalized ratio >1.5, and/or fibrinogen <300 mg/dL based on institutional protocols developed by our Division of Transfusion Medicine & Coagulation. The outcomes of those patients with and without coagulopathy were compared with appropriate adjustments. Receiver operating characteristics curves (ROCs) were constructed to assess the ability of select variables to discriminate between women with and without coagulopathy, and the area under the curves (AUCs) were calculated.

Results: Of 123 singleton patients with PAS, 37 (30.1%; 95%CI 22.1-39.0) developed coagulopathy and 86 (69.9%; 95%CI 61.0-77.9) did not. Baseline patient demographic characteristics did not differ significantly between these groups. Estimated blood loss (median and Inter-quartile range) was 2100cc (1800, 400) and 1400 (1000, 2500) in the presence and absence of coagulopathy, respectively (P < 0.01). The overall number of units of red blood cells (RBC) transfused was greatest in the coagulopathy group [3 (2, 9) vs. 1 (0, 4); P < 0.01]. Univariate regression analysis confirmed the association between coagulopathy and (i) the number of units of RBC's transfused, and (ii) the estimated blood loss. ROC curves showed that an estimated blood loss ≥ 1500 mL had the best discriminating power. Depth and/or severity of placental invasion were not associated with coagulopathy in patients with PAS.

Conclusions: Coagulopathy in patients with PAS undergoing hysterectomy is strongly associated with blood loss and replacement. It may be prudent to establish protocols that aggressively monitor for, and treat, coagulopathy when EBL exceeds 1500 mL in such surgeries, prior to the development of clinical coagulopathy which if uncorrected may lead to massive blood loss.
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http://dx.doi.org/10.1016/j.ejogrb.2019.04.026DOI Listing
June 2019

Utilization and outcomes of massive transfusion protocols in women with and without invasive placentation.

J Matern Fetal Neonatal Med 2020 Nov 1;33(21):3614-3618. Epub 2019 Mar 1.

Department of Obstetrics and Gynecology, Beth Israel Deaconess Medical Center, Boston, MA, USA.

Our objective was to compare women with and without invasive placentation for whom the massive transfusion protocol (MTP) was activated. In addition, we evaluated the differences in clinical management and blood product utilization between the two groups and described the activation of MTP over time. This is a retrospective cohort study of women for whom the MTP was activated from January 2012 through July 2016. Two groups were compared, those with invasive placentation (accreta, increta, percreta) and those without. We identified 87 women for whom the MTP was activated, the majority (62.1%) did not have invasive placentation. Women with invasive placentation were more likely to have had a prior cesarean delivery and placenta previa (both  < .001). Women with invasive placentation were more likely to undergo hysterectomy, experience more blood loss, and receive cell salvage (all  ≤ .04). Blood product utilization was similar between the two groups, with the exception of cell-salvage, which was more commonly used for women with invasive placentation. The proportion of deliveries necessitating MTP activation ranged from 1.4 to 2.6 per 1000 deliveries. Invasive placentation accounts for less than half of the cases complicated by activation of an MTP. Cases with invasive placentation were more likely to result in a vertical uterine and skin incision or a hysterectomy. With the exception of cell-salvage, blood product utilization was similar.
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http://dx.doi.org/10.1080/14767058.2019.1581168DOI Listing
November 2020

Coagulation and Bleeding Management in Pediatric Extracorporeal Membrane Oxygenation: Clinical Scenarios and Review.

Front Med (Lausanne) 2018 11;5:361. Epub 2019 Jan 11.

Division of Transfusion Medicine & Coagulation, Texas Children's Hospital, Houston, TX, United States.

Extracorporeal membrane oxygenation (ECMO) is a life-saving procedure that requires careful coagulation management. Indications for ECMO continue to expand, leading to more complicated patients treated by ECMO teams. At our pediatric institution, we utilize a Coagulation Team to guide anticoagulation, transfusion and hemostasis management in an effort to avoid the all-to-common complications of bleeding and thrombosis. This team formulates a coagulation plan in conjunction with a multidisciplinary ECMO team after careful review of all available laboratory data as well as the patient's clinical status. Here, we present our general strategies for ECMO management in various clinical scenarios and a review of the literature pertaining to coagulation management in the pediatric ECMO setting.
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http://dx.doi.org/10.3389/fmed.2018.00361DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6340094PMC
January 2019

Deficiency of complement factor H-related proteins and autoantibody-positive hemolytic uremic syndrome in an infant with combined partial deficiencies and autoantibodies to complement factor H and ADAMTS13.

Clin Kidney J 2018 Dec 7;11(6):791-796. Epub 2018 Mar 7.

Baylor College of Medicine, Houston, TX, USA.

A 3-month-old male infant developed an extremely severe episode of atypical hemolytic uremic syndrome (aHUS) associated with partial deficiencies of full-length complement factor H (FH; ∼15% of infant normal) and a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13 (ADAMTS13) (39% of normal) and autoantibodies reactive with both proteins. His FH and ADAMTS13 genes were normal, indicating that the partial deficiencies were acquired, probably as the result of autoantibodies against full-length FH and ADAMTS13. The child also had a homozygous deletion of the complement factor H-related (CFHR)3-CFHR1 portion in the complement factor H () gene cluster. He therefore had deficiency of CFHR proteins and autoantibody-positive hemolytic uremic syndrome (DEAP-HUS) with an unusual early onset associated with a partial deficiency of ADAMTS13 and an anti-ADAMTS13 autoantibody. His clinical episode of aHUS responded to plasma infusion and subsequent treatment with mycophenolate and rituximab. We believe that this is the first report of DEAP-HUS in an infant with partial deficiencies in both ADAMTS13 and full-length FH acquired in association with autoantibodies to both proteins.
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http://dx.doi.org/10.1093/ckj/sfy010DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6275444PMC
December 2018

ABO-incompatible deceased donor pediatric liver transplantation: Novel titer-based management protocol and outcomes.

Pediatr Transplant 2018 11 2;22(7):e13263. Epub 2018 Aug 2.

Section of Pediatric Allergy & Immunology, Texas Children's Hospital, Baylor College of Medicine, Houston, Texas.

ABO-ILT have re-emerged as an alternate option for select patients awaiting transplant. However, treatment protocols for children undergoing deceased donor ABO-ILT are not standardized. We implemented a novel IS protocol for children undergoing deceased donor ABO-ILT based on pretransplant IH titers. Children with high pretransplant IH titers (≥1:32) underwent an enhanced IS protocol including plasmapheresis, rituximab, IVIG, and mycophenolate, while children with IH titers ≤1:16 received steroids and tacrolimus. We retrospectively assessed our outcomes of ABO-ILT with ABO-compatible recipients of similar age and diagnosis over a 2-year period. Ten children with median age of 8.9 months underwent ABO-ILT, 4 of 10 patients underwent enhanced IS due to high IH titers. Rates of complications (rejection, infections, biliary, and vascular) at both 1 year and up to 3 years post-transplant were comparable between the groups. Patients with ABO-ILT had good graft function with 100% survival at a median follow-up of 3.3 years. In conclusion, IS tailored to pretransplant IH titers in pediatric deceased donor ABO-ILT is feasible and can achieve outcomes similar to ABO-CLT at 1 and 3 years post-transplantation.
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http://dx.doi.org/10.1111/petr.13263DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6197909PMC
November 2018

Outcomes of Planned Compared With Urgent Deliveries Using a Multidisciplinary Team Approach for Morbidly Adherent Placenta.

Obstet Gynecol 2018 02;131(2):234-241

Divisions of Maternal-Fetal Medicine and Gynecologic Oncology and Inpatient Women's Service, Department of Obstetrics and Gynecology, the Department of Pediatrics and Neonatology, the Department of Urology, and the Division of Transfusion Medicine, Department of Pathology & Immunology, Baylor College of Medicine and Texas Children's Hospital, Houston, Texas.

Objective: To compare outcomes between planned and urgent cesarean hysterectomy for morbidly adherent placenta managed by a multidisciplinary team.

Methods: This is a retrospective case-control study of women with singleton pregnancies with antenatally suspected and pathologically confirmed morbidly adherent placenta who underwent cesarean hysterectomy between January 1, 2011, and February 30, 2017. Timing of delivery was classified as either planned (delivery at 34-35 weeks of gestation) or urgent (need for urgent delivery as a result of uterine contractions, bleeding, or both). The primary outcome variable was composite maternal morbidity. Logistic regression analysis was used to evaluate risk factors for urgent delivery.

Results: One hundred thirty patients underwent hysterectomy. Sixty (46.2%) required urgent delivery. Composite maternal morbidity was identified in 34 (56.7%) of the urgent and 26 (37.1%) of the planned deliveries (P=.03). Fewer units of red blood cells and fresh frozen plasma were transfused in the planned delivery group (red blood cells, median interquartile range 3 [0-8] versus 1 [0-4], P=.02; fresh frozen plasma, median interquartile range 1 [0-2] versus 0 [0-0], P=.001). Rates of low Apgar score and respiratory distress syndrome were higher in the urgent compared with the planned delivery group (5-minute Apgar score less than 7, 34 [59.6%] versus 14 [23.3%], P<.01; respiratory distress syndrome, 34 [61.8%] versus 16 [27.1%], P<.01). A history of two or more prior cesarean deliveries was an independent predictor of urgent delivery (adjusted odds ratio 11.4, 95% CI 1.8-71.1).

Conclusion: Women with morbidly adherent placenta requiring urgent delivery have a worse outcome than women with planned delivery. Women with morbidly adherent placenta and two or more prior cesarean deliveries are at increased risk for urgent delivery. In such women, scheduling delivery before the standard 34- to 35-week timeframe may be reasonable.
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http://dx.doi.org/10.1097/AOG.0000000000002442DOI Listing
February 2018

Retrospective surveys of obstetric red cell transfusion practice in the UK and USA.

Int J Gynaecol Obstet 2017 Dec 13;139(3):342-345. Epub 2017 Sep 13.

Academic Department of Obstetrics and Gynaecology, Imperial College London, London, UK.

Objective: To examine whether professional guidance promoting a policy of restrictive blood transfusion is being followed.

Methods: A retrospective analysis of post-delivery transfusion data from 17 maternity units in the UK (1988-2000) was undertaken. Additionally, an audit was performed of women receiving one or two units of red cells 6-24 hours after delivery at three centers in the UK and USA in 2013-2016.

Results: Between 1988 and 2000, 4700 women received one or two transfusions: 303 (6.4%) received one unit and 4397 (93.6%) received two. Median estimated blood loss (EBL) was similar in both groups (600 mL [IQR 400-1000] vs 700 mL [IQR 400-1000], respectively; P=0.862]. Between 2013 and 2016, 41, 22, and 64 women received one or two units during transfusion at centers A, B, and C, respectively. Two units were transfused for 40 (97.6%) of the women in center A, 21 (95.5%) at center B, and 58 (90.6%) at center C. Median EBL was similar, irrespective of whether one or two units were given.

Conclusion: Current transfusion practice deviates from evidence-based guidelines. Either by default or longstanding tradition, more women receive two rather than one unit despite similar EBL.
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http://dx.doi.org/10.1002/ijgo.12309DOI Listing
December 2017

Multidisciplinary team learning in the management of the morbidly adherent placenta: outcome improvements over time.

Am J Obstet Gynecol 2017 06 16;216(6):612.e1-612.e5. Epub 2017 Feb 16.

Division of Maternal Fetal Medicine, Department of Obstetrics and Gynecology, Baylor College of Medicine and Texas Children's Hospital, Houston, TX.

Background: Morbidly adherent placenta (MAP) is a serious obstetric complication causing mortality and morbidity.

Objective: To evaluate whether outcomes of patients with MAP improve with increasing experience within a well-established multidisciplinary team at a single referral center.

Study Design: All singleton pregnancies with pathology-confirmed MAP (including placenta accreta, increta, or percreta) managed by a multidisciplinary team between January 2011 and August 2016 were included in this retrospective study. Turnover of team members was minimal, and cases were divided into 2 time periods so as to compare 2 similarly sized groups: T1 = January 2011 to April 2014 and T2 = May 2014 to August 2016. Outcome variables were estimated blood loss, units of red blood cell transfused, volume of crystalloid transfused, massive transfusion protocol activation, ureter and bowel injury, and neonatal birth weight. Comparisons and adjustments were made by use of the Student t test, Mann-Whitney U test, χ test, analysis of covariance, and multinomial logistic regression.

Results: A total of 118 singleton pregnancies, 59 in T1 and 59 in T2, were managed during the study period. Baseline patient characteristics were not statistically significant. Forty-eight of 59 (81.4%) patients in T1 and 42 of 59 (71.2%) patients in T2 were diagnosed with placenta increta/percreta. The median [interquartile range] estimated blood loss (T1: 2000 [1475-3000] vs T2: 1500 [1000-2700], P = .04), median red blood cell transfusion units (T1: 2.5 [0-7] vs T2: 1 [0-4], P = .02), and median crystalloid transfusion volume (T1: 4200 [3600-5000] vs T2: 3400 [3000-4000], P < .01) were significantly less in T2. Also, a massive transfusion protocol was instituted more frequently in T1: 15/59 (25.4%) vs 3/59 (5.1%); P < .01. Neonatal outcomes and surgical complications were similar between the 2 groups.

Conclusion: Our study shows that patient outcomes are improved over time with increasing experience within a well-established multidisciplinary team performing 2-3 cases per month. This suggests that small, collective changes in team dynamics lead to continuous improvement of clinical outcomes. These findings support the development of centers of excellence for MAP staffed by stable, core multidisciplinary teams, which should perform a significant number of these procedures on an ongoing basis.
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http://dx.doi.org/10.1016/j.ajog.2017.02.016DOI Listing
June 2017

Pediatric Acquired von Willebrand Syndrome in Cardiopulmonary Disorders: Do Laboratory Abnormalities Predict Bleeding Risk?

J Pediatr Hematol Oncol 2017 03;39(2):121-125

Departments of Pediatrics/Hematology Section, Transfusion Medicine & Coagulation, Baylor College of Medicine and Texas Children's Hospital, Houston, TX.

There are conflicting reports on whether or not laboratory abnormalities in pediatric acquired von Willebrand syndrome (AVWS) predict bleeding manifestations in patients with cardiopulmonary disorders (CPD). We retrospectively reviewed charts of patients with AVWS and CPD (n=16) seen at Texas Children's Hospital from 2003 to 2012. The most common CPD were valve stenoses, ventricular septal defects, and pulmonary hypertension. All patients had loss of high molecular weight multimers. Fifteen (94%) patients presented with bleeding symptoms, with menorrhagia and epistaxis being the most common. Von Willebrand ristocetin cofactor activity (VWF:RCo), as well as the use of anticoagulant or antiplatelet medication, did not predict bleeding manifestations (P=0.70 and 0.84, respectively). VWF:RCo/VWF antigen (Ag) ratio of <0.7 was significantly associated with presence of bleeding symptoms. All patients who had complete repair of their cardiac defect experienced normalization of VWF multimers and VWF:RCo/Ag ratio, as well as bleeding symptom resolution. We conclude that increased bleeding risk is associated with low VWF:RCo/Ag ratio in pediatric AVWS due to CPD. However, other laboratory abnormalities such as VWF:RCo level and qualitative multimer analysis, do not appear to predict bleeding. Future studies exploring quantification of multimer loss may be helpful in further assessing bleeding risk associations.
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http://dx.doi.org/10.1097/MPH.0000000000000738DOI Listing
March 2017

Stability and Sterility of Enoxaparin 8 mg/mL Subcutaneous Injectable Solution.

J Pediatr Pharmacol Ther 2016 Jul-Aug;21(4):322-326

Department of Pathology & Immunology, Pediatrics, Baylor College of Medicine, Houston, Texas.

Enoxaparin is often diluted to accurately deliver doses to neonatal and infant patients. Current recommendations for dilutions may not be adequate for the smallest patients. Review of dosing at our institution occurred, and an 8 mg/mL concentration of enoxaparin was chosen. A concentration of 8 mg/mL was compounded by diluting 0.4 mL of enoxaparin (100 mg/mL) into 4.6 mL of sterile water for injection into an empty sterile vial. Four syringes of the 8 mg/mL concentration were prepared by 5 technicians (20 total syringes). Stability and sterility testing occurred a 0, 7, 14, and 30 days. One-way repeated-measures analysis of variance was used to detect significant differences in Anti-Factor Xa concentrations at the testing time points. The dilution of enoxaparin was sterile at 30 days but exhibited significant degradation at the 30-day point (p < 0.05). A dilution of enoxaparin 8 mg/mL is stable and sterile for 14 days refrigerated but is not stable at 30 days.
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http://dx.doi.org/10.5863/1551-6776-21.4.322DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5040175PMC
October 2016

Neonatal transfusion models to determine the impact of using fresh red blood cells on inventory and exposure.

Blood Transfus 2015 Oct 12;13(4):595-9. Epub 2015 Jun 12.

Division of Transfusion Medicine and Coagulation, Texas Children's Hospital, Houston, United States of America.

Background: Data on age of blood and its impact on donor exposure and inventory in the paediatric setting are lacking. The standard of practice of reserving a specific red blood cell (RBC) unit for neonates who may require repeat transfusions is unique to the paediatric setting. Requiring transfusion of fresher RBC units may increase the exposure of neonates to multiple units and negatively affect the supply of fresh RBC. We constructed a transfusion model based on a 6 months of retrospective neonatal transfusion data at our institution.

Materials And Methods: All neonates (≤4 months old) at Texas Children's Hospital who received a RBC transfusion from June to November 2011 were included and RBC transfusion data were compiled. The age of blood at the time of each RBC transfusion was recorded. These data were reviewed to calculate exposure and inventory impact if each transfusion had been restricted to RBC either ≤7 or ≤14 days old at transfusion.

Results: A total of 216 neonates received 938 RBC transfusions. Of these, 393 (42%) were fresh RBC (≤14 days old), even without a required age guideline. Requiring fresh (≤14 days) RBC for all transfusions in this period would have resulted in 70 additional fresh units and one or more additional exposures in 44 patients. Requiring fresher (≤7 days old) RBC would have resulted in an additional 147 units and. one or more additional exposures in 54 patients.

Discussion: The more conservative model of fresh (≤7 days old) RBC would greatly increase fresh RBC inventory requirements, and 25% of transfused neonates would require additional RBC exposure. Based on retrospective data and the two transfusion models, it can be concluded that requiring RBC ≤14 days old for neonatal transfusion would best balance the use of fresher RBC with the smallest increase in patient exposure (20%) and minimum impact on the RBC inventory.
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http://dx.doi.org/10.2450/2015.0300-14DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4624535PMC
October 2015

Regulatory components of the alternative complement pathway in endothelial cell cytoplasm, factor H and factor I, are not packaged in Weibel-Palade bodies.

PLoS One 2015 24;10(3):e0121994. Epub 2015 Mar 24.

Department of Bioengineering, Rice University, Houston, Texas, United States of America; Baylor College of Medicine, Houston, Texas, United States of America.

It was recently reported that factor H, a regulatory component of the alternative complement pathway, is stored with von Willebrand factor (VWF) in the Weibel-Palade bodies of endothelial cells. If this were to be the case, it would have therapeutic importance for patients with the atypical hemolytic-uremic syndrome that can be caused either by a heterozygous defect in the factor H gene or by the presence of an autoantibody against factor H. The in vivo Weibel-Palade body secretagogue, des-amino-D-arginine vasopressin (DDAVP), would be expected to increase transiently the circulating factor H levels, in addition to increasing the circulating levels of VWF. We describe experiments demonstrating that factor H is released from endothelial cell cytoplasm without a secondary storage site. These experiments showed that factor H is not stored with VWF in endothelial cell Weibel-Palade bodies, and is not secreted in response in vitro in response to the Weibel-Palade body secretagogue, histamine. Furthermore, the in vivo Weibel-Palade body secretagogue, DDAVP does not increase the circulating factor H levels concomitantly with DDAVP-induced increased VWF. Factor I, a regulatory component of the alternative complement pathway that is functionally related to factor H, is also located in endothelial cell cytoplasm, and is also not present in endothelial cell Weibel-Palade bodies. Our data demonstrate that the factor H and factor I regulatory proteins of the alternative complement pathway are not stored in Weibel-Palade bodies. DDAVP induces the secretion into human plasma of VWF--but not factor H.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0121994PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4372330PMC
February 2016

Plasma is ineffective in correcting mildly elevated PT-INR in critically ill children: a retrospective observational study.

J Intensive Care 2014 29;2(1):64. Epub 2014 Nov 29.

Division of Transfusion Medicine and Coagulation, Texas Childrens' Hospital, 6621 Fannin Street, Suite WB 1100, Houston, TX 77030 USA ; Department of Pathology and Immunology, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030 USA.

Background: Fresh frozen plasma transfusion is widely utilized in pediatric clinical practice to correct mild coagulopathy. Several studies on adult population have shown that transfusion of plasma cannot effectively correct mild coagulopathy when international normalized ratio (INR) is ≤1.5. Much controversy exists about the generalization of this finding for pediatric populations, especially since pediatric dosages often exceed those in adults. The aim of this study is to determine the prevalence of plasma transfusion with mild coagulopathy (INR ≤ 1.5) and its effectiveness in a pediatric setting.

Methods: In our tertiary referral hospital, we retrospectively reviewed the electronic medical records of all patients who received plasma (April to October 2011) for mildly elevated prothrombin time (PT)-INR levels (≤1.5) and had post-transfusion PT-INR measurements; patients who received intraoperative, ECMO, or plasma exchange-related plasma transfusions were excluded from this study. We abstracted demographic data and pre- and post coagulation test results for the patients included in our study.

Results: Among 468 plasma transfusions administered to 285 patients from April to June 2011, 60 plasma transfusions (12.8%) were given to patients with PT-INR ≤ 1.5 (range 1.3-1.5). Forty-one patients [median age 2.5 years (IQR, 0.14 to 13.75 years), median weight of 16.0 kg (IQR, 8.0 to 69.3 kg)] who received 41 single plasma transfusions [median dose 11 mL/Kg (IQR, 6-15)] had post-transfusion PT-INR measurements and were included in our study. There was no significant difference in their PT-INR values (p = 0.34) pre- and post-transfusion. Of our study, only 15.4% patients showed post-transfusion normalization [median change in PT-INR 0.15 (IQR, 0.1-0.2)] and were not different from the remaining 85% in age, plasma dose, and bleeding status.

Conclusions: The prevalence of plasma transfusion for correction of mildly elevated PT-INR levels in critically ill children is high (12.8%). Plasma transfusion showed no significant effect in correcting minor prolongation of PT-INR in pediatric patients regardless of age, volume of plasma transfused per kilogram (dosage), or bleeding status.
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http://dx.doi.org/10.1186/s40560-014-0064-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4336132PMC
February 2015

Maternal morbidity in patients with morbidly adherent placenta treated with and without a standardized multidisciplinary approach.

Am J Obstet Gynecol 2015 Feb 27;212(2):218.e1-9. Epub 2014 Aug 27.

Division of Maternal-Fetal Medicine, Department of Obstetrics and Gynecology, Baylor College of Medicine and Texas Children's Hospital, Houston, TX.

Objective: The purpose of this study was to test the hypothesis that a standardized multidisciplinary treatment approach in patients with morbidly adherent placenta, which includes accreta, increta, and percreta, is associated with less maternal morbidity than when such an approach is not used (nonmultidisciplinary approach).

Study Design: A retrospective cohort study was conducted with patients from 3 tertiary care hospitals from July 2000 to September 2013. Patients with histologically confirmed placenta accreta, increta, and percreta were included in this study. A formal program that used a standardized multidisciplinary management approach was introduced in 2011. Before 2011, patients were treated on a case-by-case basis by individual physicians without a specific protocol (nonmultidisciplinary group). Estimated blood loss, transfusion of packed red blood cells, intraoperative complications (eg, vascular, bladder, ureteral, and bowel injury), neonatal outcome, and maternal postoperative length of hospital stay were compared between the 2 groups.

Results: Of 90 patients with placenta accreta, 57 women (63%) were in the multidisciplinary group, and 33 women (37%) were in the nonmultidisciplinary group. The multidisciplinary group had more cases with percreta (P = .008) but experienced less estimated blood loss (P = .025), with a trend to fewer blood transfusions (P = .06), and were less likely to be delivered emergently (P = .001) compared with the nonmultidisciplinary group. Despite an approach of indicated preterm delivery at 34-35 weeks of gestation, neonatal outcomes were similar between the 2 groups.

Conclusion: The institution of a standardized approach for patients with morbidly adherent placentation by a specific multidisciplinary team was associated with improved maternal outcomes, particularly in cases with more aggressive placental invasion (increta or percreta), compared with a historic nonmultidisciplinary approach. Our standardized approach was associated with fewer emergency deliveries.
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http://dx.doi.org/10.1016/j.ajog.2014.08.019DOI Listing
February 2015

Integration of the transfusion medicine and coagulation services.

Transfusion 2014 May;54(5):1440-1

Division of Transfusion Medicine & Coagulation, Texas Children's Hospital, Houston, TX; Department of Pathology and Immunology, Baylor College of Medicine, Houston, TX.

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http://dx.doi.org/10.1111/trf.12551DOI Listing
May 2014

Age-based difference in activation markers of coagulation and fibrinolysis in extracorporeal membrane oxygenation.

Pediatr Crit Care Med 2014 Jun;15(5):e198-205

1Section of Neonatology, Baylor College of Medicine, Texas Children's Hospital, Houston, TX. 2Department of Pediatrics, Baylor College of Medicine, Texas Children's Hospital, Houston, TX. 3Department of Pathology & Immunology, Baylor College of Medicine, Texas Children's Hospital, Houston, TX. 4Cancer and Hematology Centers, Baylor College of Medicine, Texas Children's Hospital, Houston, TX. 5Department of Medicine, Baylor College of Medicine, Texas Children's Hospital, Houston, TX.

Objective: Coagulation system activation in extracorporeal membrane oxygenation results in hemostatic derangements. Thrombin generation markers like prothrombin fragment 1+2 and thrombin-antithrombin complex are sensitive markers of hypercoagulability. Plasmin-antiplasmin complex is a sensitive marker for fibrinolysis. D-dimers reflect thrombin generation and fibrinolysis. The aim was to identify the extent of hemostasis activation during extracorporeal membrane oxygenation by measuring thrombin-antithrombin complex, prothrombin fragment 1+2, plasmin-antiplasmin complex, and D-dimer.

Design: Prospective cohort study.

Setting: Tertiary care academic center.

Patients: Children placed on extracorporeal membrane oxygenation from April 2011 to January 2013.

Interventions: Prothrombin fragment 1+2, thrombin-antithrombin complex, plasmin-antiplasmin complex, and D-dimer were measured on days 1 and 5 of extracorporeal membrane oxygenation.

Measurements And Main Results: Data presented as median (interquartile range); nonparametric tests were done using SPSS. Twenty-nine children (52% < 30 d old [neonates], median extracorporeal membrane oxygenation length 151 hr) were studied. Complications included thrombosis in 14%, bleeding in 45%, and thrombosis and bleeding together in 10%. Thrombin-antithrombin complex, prothrombin fragment 1+2, plasmin-antiplasmin complex, and D-dimer levels were high on day 1 and remained increased on extracorporeal membrane oxygenation. In neonates, all levels were higher on day 5 compared with day 1: thrombin-antithrombin complex (55.6 μg/L [30.7-76.0] vs 18.7 μg/L [10.9-34.6]; p = 0.03), prothrombin fragment 1+2 (2,038 pmol/L [1,093-4,018.5] vs 377.5 pmol/L [334.3-1,103.0]; p = 0.00), plasmin-antiplasmin complex (2,160 μg/L [786-3,090] vs 398 μg/L [296.8-990.8]; p = 0.00), and D-dimer (3.0 μg/mL [1.9-11.5] vs 1.5 μg/mL [0.6-2.9]; p = 0.01). Thrombin-antithrombin complex, prothrombin fragment 1+2, plasmin-antiplasmin complex, and D-dimer levels did not correlate with anti-Xa activity or heparin dose. In bleeders older than 30 days, plasmin-antiplasmin complex stayed elevated on day 5, but in patients with no bleeding complications, plasmin-antiplasmin level showed a declining trend. In neonates, plasmin-antiplasmin levels increased over the course of extracorporeal membrane oxygenation irrespective of bleeding.

Conclusion: Despite our best efforts at adequate anticoagulation with unfractionated heparin, neonates showed persistent increase in coagulation activation on extracorporeal membrane oxygenation. Fibrinolysis activation may contribute to bleeding in patients older than 30 days. Different anticoagulation protocols should be individualized based on age.
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http://dx.doi.org/10.1097/PCC.0000000000000107DOI Listing
June 2014

Granulocyte transfusions for children with infection and neutropenia or granulocyte dysfunction.

Pediatr Hematol Oncol 2014 Aug 2;31(5):425-34. Epub 2014 Jan 2.

1Department of Pediatrics, Texas Children's Hospital , Houston, TX , USA.

Transfusions of granulocytes can be used as an adjunct therapy to antimicrobials in patients with infection and neutropenia or granulocyte dysfunction. However, there is a lack of strong clinical evidence to support the use of this treatment strategy, particularly in children. We retrospectively reviewed the medical records of children who received granulocytes at our institution from April 2009 to October 2012, with emphasis on primary indication for the transfusion and clinical outcome in terms of infection. The patients had granulocyte dysfunction or severe neutropenia, defined as absolute neutrophil count (ANC) < 500 cells/mm(3) due to chemotherapy or hematopoietic stem cell transplant (HSCT), and reasonable hope for bone marrow recovery or engraftment. Eighteen children received granulocytes during 20 distinct episodes: 62% (n = 13) for acute infection, 29% (n = 5) for unresolved chronic infection during the time of HSCT, and 9% (n = 2) for other clinical conditions such as typhilitis and appendectomy. Overall, 92% (n = 12) of the episodes of acute infection had complete or partial resolution, as determined by review of vital signs, physical exam findings and discontinuation of antimicrobials. A substantial number (46%) of children who received granulocytes for acute infection developed respiratory adverse events, but all of these recovered. We conclude that granulocyte transfusions continue to be primarily used in neutropenic patients with acute infections, and that its use in this group of patients is reasonable. However, a prospective randomized clinical trial is needed to evaluate safety and whether the use of granulocytes is superior to antimicrobial-only therapy.
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http://dx.doi.org/10.3109/08880018.2013.868562DOI Listing
August 2014

An algorithmic approach to coagulation testing.

Dis Mon 2012 Aug;58(8):431-9

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http://dx.doi.org/10.1016/j.disamonth.2012.04.006DOI Listing
August 2012