Early viscoelastometric guided fibrinogen replacement combined with escalation of clinical care reduces progression in postpartum haemorrhage: a comparison of outcomes from two prospective observational studies.

BACKGROUND: Viscoelastometric haemostatic assays (VHA) give rapid information on coagulation status, allowing individualised resuscitation. METHODS: This paper compares outcomes from two observational studies of postpartum haemorrhage (PPH) in the same institution, before and after practice changed from fixed ratio empirical transfusion of coagulation products with laboratory coagulation testing to VHA-guided fibrinogen replacement incorporated into an enhanced PPH care bundle. In both studies, all blood samples were taken near 1000 mL qualitative blood loss (QBL). In Study One, QBL started once PPH was identified, and resuscitation with coagulation blood products was empirical or based on laboratory tests of coagulation. In Study Two, QBL started at delivery and VHA was used to guide fibrinogen replacement if FIBTEM A5 was <12 mm (Claus fibrinogen ≤2 g/L) or to withhold coagulation products if FIBTEM A5 was >12 mm. RESULTS: Improved PPH outcomes were observed in Study Two, with rates of measured blood loss ≥2500 mL, ≥4 units red blood cell (RBC) transfusion, fresh frozen plasma transfusion and ≥8 units of any blood product transfusion all reduced (P < 0.01). Clinically significant improvements occurred in women with fibrinogen ≤2 g/L at study entry, where the proportion of women who received ≥4 units RBC transfusion fell from 67% in Study One to 0% in Study Two (P = 0.0007). CONCLUSIONS: These results suggest that use of VHA as part of an early bundle of PPH care targeting fibrinogen ≤2 g/L with fibrinogen concentrate reduces PPH progression. The greatest benefit was seen when fibrinogen levels were ≤2 g/L at first testing.

A description of the coagulopathy characteristics in amniotic fluid embolism: a case report.

Amniotic fluid embolism is frequently associated with coagulopathy. However, the exact nature and evolution of the bleeding disorder is incompletely understood. We report a case of clinically diagnosed amniotic fluid embolism associated with major haemorrhage and coagulopathy. We measured sequential levels of all individual clotting factors, thrombin generation, fibrinogen, and D-dimer levels over the course of the event, beginning shortly after the patient's initial collapse and during the subsequent resuscitation, to identify the specific abnormalities of coagulation from stored blood samples. A better understanding of amniotic fluid embolism and the associated coagulopathy is an important area of research to inform targeted treatment of the coagulopathy and improve outcomes for patients.

Comparison of haematological indices and transfusion management in severe and massive postpartum haemorrhage: analysis of a two-year national prospective observational study.

INTRODUCTION: This two-year prospective cohort study compared the management of women experiencing severe or massive postpartum haemorrhage (PPH) to explore the impact of targeted blood product administration on reducing PPH progression (from >1500 mL to ≥2500 mL blood loss). During the study, viscoelastic haemostatic assays (VHA) guided blood product transfusion. METHODS: All women experiencing blood loss after PPH >1000 mL were included in a national database. Haematological indices, transfusion and PPH aetiology were analysed in severe (>1500 mL blood loss or transfusion of any blood product) and massive PPH (≥2500 mL blood loss or transfusion ≥5 units red blood cells). RESULTS: Of the 61 094 maternities in Wales (2017 to 2018), 2111 had severe and 349 massive PPH. Red blood cells were transfused to 42.5% severe and 80.6% massive PPH cases. Hypofibrinogenaemia (fibrinogen <2 g/L and/or Fibtem A5 <12 mm) was the most frequent coagulation abnormality, occurring in 5.4% severe and 17.0% massive PPH, with blood coagulation products (fresh frozen plasma, platelets, cryoprecipitate and/or fibrinogen concentrate) administered to 3.6% and 22.9%. Women with hypofibrinogenaemia received targeted fibrinogen replacement in 97.8% severe and 93.6% massive PPH. The only aetiology with similar rates of hypofibrinogenaemia in severe and massive PPH was abruption (40.0% and 36.8%). CONCLUSION: Hypofibrinogenaemia was less frequent in severe PPH, although coagulopathy was observed across a range of PPH aetiologies, highlighting the importance of coagulation testing for all. Cases of abruption in severe and massive PPH had similar rates of hypofibrinogenaemia. Early VHA-guided fibrinogen replacement may reduce PPH progression in abruption and requires further evaluation.

Introduction of standardized, cumulative quantitative measurement of blood loss into routine maternity care.

INTRODUCTION: Postpartum hemorrhage (PPH) is the leading cause of maternal morbidity in the UK. Visual estimation of blood loss is unreliable yet remains common practice. As part of a national quality improvement project to improve care during PPH, standardized, quantitative measurement of blood loss (QBL) for all deliveries was introduced into a tertiary obstetric unit in Cardiff, Wales. METHODS: Retrospective analysis of 875 consecutive maternities between December 2017 and February 2018 was undertaken. Of these, 372 mothers had both pre- and post-partum hemoglobin (Hb) were recorded. Regression analyses were performed to investigate the relationship between change in Hb adjusted for red cell transfusion and QBL. RESULTS: The correlation coefficient between QBL and adjusted change in Hb for all deliveries (n = 372) was 0.57. This corresponded to an estimated fall of adjusted change in Hb of 15.3 g/L (95% CI: 13.1, 17.6) per 1000 mL blood loss. DISCUSSION: QBL has been shown to be reliable across all maternity settings, with reproducible results in theater and delivery rooms (on the obstetric unit and alongside midwifery-led unit). QBL is moderately correlated with adjusted change in Hb for all volumes of bleeding and gives clinicians more accurate knowledge of blood loss than visual estimation. This low-cost, low-fidelity intervention can influence the timely escalation of clinical care and therefore patient outcome.

The sensitivity and specificity of rotational thromboelastometry (ROTEM) to detect coagulopathy during moderate and severe postpartum haemorrhage: a prospective observational study.

INTRODUCTION: Point-of-care viscoelastic haemostatic assays such as rotational thromboelastometry (including ROTEM and TEG) have been used in the management of postpartum haemorrhage (PPH). This study compared results obtained from the automated ROTEM Sigma with laboratory tests of coagulation and platelet count during PPH. METHODS: A prospective observational cohort study recruited women with PPH ≥1000 mL (or clinical concern of bleeding). The Fibtem A5, Extem CT and Pltem (Extem A5 - Fibtem A5) results were compared with laboratory tests of fibrinogen, prothrombin time (PT), activated partial thromboplastin time (APTT) and platelet count. RESULTS: 521 women were recruited, including 274/277 (98.9%) of women with PPH ≥1500 mL. Fibtem A5 results were matched with laboratory fibrinogen in 552/644 (85.7%) samples. The incidence of abnormal laboratory results was low: fibrinogen ≤2 g/L 23/464 (5.0%), PT or APTT >1.5 × midpoint of reference range 4/464 (0.9%), and platelet count <75 × 109/L 11/477 (2.3%). Area-under-the-receiver operator characteristic curve for Fibtem A5 to detect fibrinogen ≤2 g/L was 0.96 (95% Confidence Interval (CI) 0.94 to 0.98, P<0.001), with sensitivity and specificity of Fibtem A5 ≤11 mm to detect fibrinogen ≤2 g/L of 0.76 and 0.96. Prolonged Extem CT results improved after treatment of hypofibrinogenaemia alone. Intervention points for platelet and fresh frozen plasma (FFP) transfusion based on ROTEM Sigma parameters could not be established. CONCLUSION: During PPH (≥1000 mL or cases of clinical concern about bleeding), ROTEM Sigma Fibtem A5 can detect fibrinogen ≤2 g/L and guide targeted fibrinogen replacement. Laboratory results should continue to be used to guide platelet and FFP transfusion.

Utility of viscoelastography with TEG 6s to direct management of haemostasis during obstetric haemorrhage: a prospective observational study.

BACKGROUND: The TEG 6s is an automated cartridge-based device with limited description of use in obstetric haemorrhage. The aim of this analysis was to describe the utility of TEG 6s in identifying abnormal laboratory results of coagulation and platelet count, and inform an interventional treatment algorithm for postpartum haemorrhage. METHODS: A prospective observational cohort study of 521 women with moderate to severe obstetric haemorrhage (>1000 mL blood loss), including 372 women with at least one TEG 6s test. A non-pregnant control group was used for reference. TEG 6s test parameters Citrated Functional Fibrinogen (CFF), Citrated Kaolin TEG (CK) and Citrated Rapid TEG (CRT) were compared with paired laboratory tests of fibrinogen, PT/aPTT and platelet count, obtained during haemorrhage. RESULTS: Among 456 TEG 6s tests, 389 were matched with laboratory coagulation results. The receiver operator characteristic area-under-the-curve (95% CI) for CFF amplitude by 10 min to detect Clauss fibrinogen ≤2 g/L was 0.95 (0.91 to 0.99) (P<0.0001, sensitivity 0.74 and specificity 0.97 at ≤17 mm). False positives had median (IQR) Clauss fibrinogen of 2.4 (2.3-2.7) g/L. The CK-R time had some utility for detecting prolonged PT/aPTT, however a threshold for fresh frozen plasma transfusion was not established. A CRT maximum amplitude <57 mm, when CFF was ≥15 mm, identified four of eight samples with platelet count <75 × 109/L. CONCLUSION: The TEG 6s CFF can be used to identify low fibrinogen during obstetric haemorrhage. A value to identify transfusion thresholds for PT/aPTT and platelets was not established, and laboratory results should continue to be used.

The incidence, aetiology, and coagulation management of massive postpartum haemorrhage: a two-year national prospective cohort study.

INTRODUCTION: Between 2017 and 2018 a national quality improvement initiative was introduced incorporating point-of-care viscoelastic haemostatic assays (VHA) to guide blood product transfusion. Laboratory coagulation profiles, use and results of VHA, and administration of blood products were investigated. METHODS: A two-year prospective cohort study of maternal outcomes of women experiencing massive postpartum haemorrhage (PPH) >1000 mL in Wales. In this study, cases of massive PPH (≥2500 mL and/or ≥5 units red blood cell (RBC) transfusion) were identified. RESULTS: Massive PPH occurred in 349 of 60 914 maternities (rate 5.7 per 1000). There were no deaths from PPH. Intensive care unit admission and/or hysterectomy occurred in 34/311 (10.9%) and 16/347 (4.6%), respectively. The leading cause of massive PPH was genital tract trauma (107/349, 30.6%). Two hundred and seventy-nine (80.6%) required RBC transfusion and 79/345 (22.9%) received at least one blood coagulation product. Results of VHA were recorded in 245/349 (70.2%), with 44/98 (44.9%) women tested in the first six months vs 63/77 (81.8%) in the final six months. Hypofibrinogenaemia (Clauss fibrinogen <2 g/L or FIBTEM A5 <12 mm) was observed in 56/328 (17.1%) of women, thrombocytopaenia (count <75 × 109/L) in 17/334 (5.1%) and either PT or aPTT >1.5×reference range in 10/293 (3.4%). CONCLUSION: In Wales, the use of VHA in cases of massive PPH increased over time, enabling clinicians to adopt a targeted, patient-specific approach to blood product administration, with only 22.9% of women receiving blood coagulation products and 17.1% having a documented clotting abnormality.

When does obstetric coagulopathy occur and how do I manage it?

Anticipating obstetric coagulopathy is important when obstetric anaesthetists are involved in the clinical management of women with postpartum haemorrhage. Although the incidence of coagulopathy in women with postpartum haemorrhage is low, significant hypofibrinogenaemia is associated with major haemorrhage-related morbidity and thus early identification and treatment is essential to improve outcomes. Point-of-care viscoelastic haemostatic assays, including thromboelastography and rotational thromboelastometry, provide granular information about alterations in clot formation and hypofibrinogenaemia, allow near-patient interpretation of coagulopathy, and can guide goal-directed treatment. If these assays are not available, anaesthetists should closely monitor the maternal coagulation profile with standard laboratory testing during the active phase of postpartum bleeding in order to rule coagulopathy 'in or out', decide if pro-haemostatic therapies are indicated, and assess the response to haemostatic support.

Safety guideline: neurological monitoring associated with obstetric neuraxial block 2020: A joint guideline by the Association of Anaesthetists and the Obstetric Anaesthetists' Association.

Serious neurological lesions such as vertebral canal haematoma are rare after obstetric regional analgesia/anaesthesia, but early detection may be crucial to avoid permanent damage. This may be hampered by the variable and sometimes prolonged recovery following 'normal' neuraxial block, such that an underlying lesion may easily be missed. These guidelines make recommendations for the monitoring of recovery from obstetric neuraxial block, and escalation should recovery be delayed or new symptoms develop, with the aim of preventing serious neurological morbidity.

Management of postpartum haemorrhage: from research into practice, a narrative review of the literature and the Cardiff experience.

Postpartum haemorrhage (PPH) is caused by obstetric complications but may be exacerbated by haemostatic impairment. In a 10-year programme of research we have established that haemostatic impairment is uncommon in moderate PPH and that fibrinogen falls earlier than other coagulation factors. Laboratory Clauss fibrinogen and the point-of-care surrogate measure of fibrinogen (FIBTEM A5 measured on the ROTEM® machine) are predictive biomarkers for progression from early to severe PPH, the need for blood transfusion and invasive procedures to control haemorrhage. Fibrinogen replacement is not required in PPH unless the plasma level falls below 2 g/L or the FIBTEM A5 is below 12 mm. Deficiencies of coagulation factors other than fibrinogen are uncommon even during severe PPH, and ROTEM® monitoring can inform withholding FFP safely in most women. In the absence of placental abruption, clinically significant thrombocytopenia is uncommon unless the platelet count is low before the bleed started, or very large bleeds (>5000 mL) occur. Measuring blood loss is feasible in routine practice during PPH and is more accurate than estimation. These research findings have been collated to design an ongoing quality improvement programme for all maternity units in Wales called OBS Cymru (Wales) (The Obstetric Bleeding Strategy for Wales).

Outcomes following the surgical management of left ventricular outflow tract obstruction; A systematic review and meta-analysis.

BACKGROUND: Left ventricular outflow tract obstruction (LVOTO) causes exertional symptoms in two thirds of patients with hypertrophic cardiomyopathy (HCM). Consensus guidelines recommend surgical intervention in patients with drug refractory symptoms. The primary aim of this study was to perform a systematic review and meta-analysis to determine morbidity and mortality after surgery. METHODS: Study Selection: Studies reporting outcomes following surgical intervention for symptomatic LVOTO in HCM. DATA EXTRACTION: Articles from searching two scientific databases (PubMed and Web of Science) were reviewed and data were extracted by two investigators. Meta-analysis of data was performed with heterogeneity assessed using I2 statistic. RESULTS: 85 studies were included in the systematic review and 35 studies in the meta-analysis. Contemporary early (<30 days) and late (>30 days) mortality following septal myectomy were 1.4% (CI 0.8, 2.4) I2 9.0%, p = 0.36 and 0.7% (CI 0.3, 1.2) I2 70.7%, p < 0.05 respectively. Sixty-eight studies (80%) reported perioperative complications. The contemporary rate of a perioperative ventricular septal defect was 1.4% (0.8, 2.3) I2 0%, p < 0.05. Late morbidities including atrial fibrillation, stroke, heart failure and transplant were reported in fewer than 22% of studies and few studies compared mortality and clinical outcomes using different surgical approaches to LVOTO. The incidence rate (IR) of reintervention with a further surgical procedure was 0.3% (CI 0.2, 0.4) I2 52.5%, p < 0.05. CONCLUSIONS: Contemporary surgical management of LVOTO is associated with low operative mortality rates but further studies are needed to investigate the impact of surgical therapy on non-fatal early and late complications.

Viscoelastometric-guided early fibrinogen concentrate replacement during postpartum haemorrhage: OBS2, a double-blind randomized controlled trial.

BACKGROUND: Postpartum haemorrhage (PPH) can be exacerbated by haemostatic failure. We hypothesized that early fibrinogen replacement, guided by viscoelastometric testing, reduces blood product usage and bleed size. METHODS: Women with PPH 1000-1500 ml were enrolled. If Fibtem A5 was ≤15 mm and bleeding continued, subjects were randomized to fibrinogen concentrate or placebo. The primary outcome compared the number of units of red blood cells, plasma, cryoprecipitate and platelets transfused. RESULTS: Of 663 women enrolled 55 were randomized. The adjusted incidence rate ratio (IRR) (95% CI) for the number of allogeneic units transfused in the fibrinogen group compared with placebo was 0.72 (0.3-1.7), P =0.45. In pre-specified subgroup analyses, subjects who had a Fibtem A5 ≤12 mm at the time of randomization and who received fibrinogen concentrate received a median (25th-75th centile) of 1 (0-4.5) unit of allogeneic blood products and had an additional 300 (100-350) ml blood loss whereas those who received placebo also received 3 (0-6) units of allogeneic blood products and had 700 (200-1550) ml additional blood loss; these differences were not statistically significantly different. There was one thrombotic event in each group. CONCLUSIONS: Infusion of fibrinogen concentrate triggered by Fibtem A5 ≤15 mm did not improve outcomes in PPH. Pre-specified subgroup analyses suggest that fibrinogen replacement is not required if the Fibtem A5 is > 12 mm or Clauss fibrinogen >2 g litre -1 , but an effect below these levels cannot be excluded. The raised fibrinogen at term appears to be a physiological buffer rather than required for haemostasis. TRIAL REGISTRATION: ISRCTN46295339 ( http://www.isrctn.com/ISRCTN46295339 , last accessed 5 July 2017), EudraCT 2012-005511-11 ( https://www.clinicaltrialsregister.eu/ctr-search/search?query=2012-005511-11 , last accessed 5 July 2017).

Viscoelastometry guided fresh frozen plasma infusion for postpartum haemorrhage: OBS2, an observational study.

BACKGROUND: Postpartum haemorrhage (PPH) can be exacerbated by haemostatic failure. Based on data from trauma studies, empirical infusions of fresh frozen plasma (FFP) are often given during severe PPH if coagulation tests are unavailable. This study observed a cohort of women with moderate/severe PPH in whom FFP infusion was guided by the use of viscoelastometric point-of-care testing (VE-POCT) and clinical assessment. METHODS: Women were enrolled into this observational study when blood loss was measured or suspected to be about 1000 mL. If Fibtem A5 determined by Rotem ® thromboelastometry remained >15 mm, or bleeding stopped, FFP was withheld. If Fibtem A5 was ≤15 mm and bleeding ongoing, women were randomized into an interventional study as previously reported. Clinical and laboratory outcomes were recorded. RESULTS: The study recruited 605 women and 98% had FFP withheld. The median (25 th -75 th centile) total blood loss was 1500 (1300-2000) mL with 300 (50-545) mL occurring after enrolment. Total blood loss was >2500 mL in 40/605 (6.6%) women. RBCs were transfused in 141/605 (23.3%) patients and 11 (1.8%) received ≥4 units. At least one invasive procedure was performed in 283/605 (46.8%) women. Level 3 care was required for 10/605 (1.7%) women. No women developed clinically significant haemostatic impairment. CONCLUSIONS: Restrictive use of FFP guided by clinical assessment of bleeding and VE-POCT is feasible and did not result in clinically significant haemostatic impairment. Studies should compare the clinical and cost effectiveness of empirical FFP infusions, according to current guidelines, with targeted use of FFP based on VE-POCT. CLINICAL TRIAL REGISTRATION: ISRCTN46295339 ( http://www.isrctn.com/ISRCTN46295339 ) (accessed July 24, 2017), EudraCT 2012-005511-11 ( https://www.clinicaltrialsregister.eu/ctr-search?query=2011-005511-11 ) (accessed July 24, 2017).

Sudden cardiac death in inherited cardiomyopathy.

Cardiomyopathy is an important cause of sudden cardiac death particularly in adolescents and young adults. The risk of sudden cardiac death varies between individual cardiomyopathies and is dependent on the severity of disease, age and gender. Although rare in cardiomyopathies, a fundamental aspect of clinical management is a systematic and thorough clinical assessment to identify the small number of individuals who are at risk and who can be protected with prophylactic ICD therapy.

Platelet count and transfusion requirements during moderate or severe postpartum haemorrhage.

Limited data exist on platelet transfusion during postpartum haemorrhage. We retrospectively analysed a consecutive cohort from a single centre of 347 women with moderate or severe postpartum haemorrhage, transfused according to national guidelines. Twelve (3%) women required a platelet transfusion. There were no differences between women who did and did not receive platelets with respect to age, mode of initiation of labour or mode of delivery. Women receiving a platelet transfusion had a lower median (IQR [range]) platelet count at study entry than women who did not receive platelets before haemorrhage (135 (97-175 [26-259])×10(9) .l(-1) vs 224 (186-274 [91-1006])×10(9) .l(-1) ), respectively), and at diagnosis of postpartum haemorrhage (median 114 (78-153 [58-238])×10(9) .l(-1) vs 193 (155-243 [78-762])×10(9) .l(-1) respectively). Six women were thrombocytopenic pre-delivery. The cause of haemorrhage that was associated with the highest rate of platelet transfusion was placental abruption, with three of 14 women being transfused. If antenatal thrombocytopenia or consumptive coagulopathy were not present, platelets were only required for haemorrhage > 5000 ml. Early formulaic platelet transfusion would have resulted in many women receiving platelets unnecessarily. Using current guidelines, the need for platelet transfusion is uncommon without antenatal thrombocytopenia, consumptive coagulopathy or haemorrhage > 5000 ml. We found no evidence to support early fixed-ratio platelet transfusion.

AAGBI guidelines: the use of blood components and their alternatives 2016.

Blood transfusion can be life-saving. Anaesthetists regularly request and administer blood components to their patients. All anaesthetists must be familiar with indications and appropriate use of blood and blood components and their alternatives, but close liaison with haematology specialists and their local blood sciences laboratory is encouraged. Considerable changes in approaches to optimal use of blood components, together with the use of alternative products, have become apparent over the past decade, leading to a need to update previous guidelines and adapt them for the use of anaesthetists working throughout the hospital system.