Management of coagulopathy associated with postpartum hemorrhage: guidance from the SSC of the ISTH
2015; Elsevier BV; Volume: 14; Issue: 1 Linguagem: Inglês
10.1111/jth.13174
ISSN1538-7933
AutoresP. Collins, Rezan A. Kadir, Jecko Thachil,
Tópico(s)Trauma and Emergency Care Studies
ResumoPostpartum hemorrhage (PPH) caused an estimated 78 000 maternal deaths worldwide in 2012 http://www.who.int/mediacentre/factsheets/fs348/en/ accessed 11 May 2015 1.Lennox C, Marr L. Scottish confidential audit of severe maternal morbidity. 9th Annual Report (data from 2011). http://healthcareimprovementscotland.org/his/idoc.ashx?docid=5fb640e2-d079-48cc-ad49-a58f6929b685&version=-1. 2013. Accessed 16 November 2015.Google Scholar, 2.Say L. Chou D. Gemmill A. Tunçalp Ö. Moller A.B. Daniels J. Gülmezoglu A.M. Temmerman M. Alkema L. Global causes of maternal death: a WHO systematic analysis.Lancet Glob Health. 2014; 2: e323-33Abstract Full Text Full Text PDF PubMed Scopus (2824) Google Scholar. In addition to optimizing obstetric management, correction of any coagulopathy is likely to improve outcomes. The key to good outcomes is comprehensive local protocols for early recognition and treatment of PPH by senior clinicians 3.Royal College of Obstetricians and Gynaecologists. Prevention and management of postpartum haemorrhage. Green‐top guideline No. 52, 2009. http://www.rcog.org.uk/files/rcog-corp/GT52PostpartumHaemorrhage0411.pdf 2013. Accessed 16 November 2015.Google Scholar, 4.Shields L.E. Wiesner S. Fulton J. Pelletreau B. Comprehensive maternal hemorrhage protocols reduce the use of blood products and improve patient safety.Am J Obstet Gynecol. 2015; 212: 272-80Abstract Full Text Full Text PDF PubMed Scopus (144) Google Scholar. There are limited data on how best to assess and correct abnormalities of hemostasis during PPH and this guidance gives a pragmatic approach. The wording ‘we recommend’ indicates a strong consensus among the panel members, whereby the clinician should consider adopting the practice in most cases. ‘We suggest’ reflects a weak guidance statement with moderate consensus among the panel members, whereby the clinician may adopt the guidance or use an alternative approach. At term increased levels of procoagulant factors and decreases in anticoagulants induce a prothrombotic state 5.Allard S. Green L. Hunt B.J. How we manage the haematological aspects of major obstetric haemorrhage.Br J Haematol. 2014; 164: 177-88Crossref PubMed Scopus (39) Google Scholar. Coagulopathies associated with PPH differ from those associated with trauma‐induced massive hemorrhage. The etiology of the coagulopathy of PPH relates to varying proportions of dilutional coagulopathy, localized consumption, disseminated consumption and/or increased fibrinolysis (Fig. S1) 5.Allard S. Green L. Hunt B.J. How we manage the haematological aspects of major obstetric haemorrhage.Br J Haematol. 2014; 164: 177-88Crossref PubMed Scopus (39) Google Scholar, 6.Collis R.E. Collins P.W. Haemostatic management of obstetric haemorrhage.Anaesthesia. 2015; 70: 78-86Crossref PubMed Google Scholar, 7.Levi M. Pathogenesis and management of peripartum coagulopathic calamities (disseminated intravascular coagulation and amniotic fluid embolism).Thromb Res. 2013; 131: S32-4Abstract Full Text PDF PubMed Scopus (30) Google Scholar, 8.Thachil J. Toh C.H. Disseminated intravascular coagulation in obstetric disorders and its acute haematological management.Blood Rev. 2009; 23: 167-76Crossref PubMed Scopus (124) Google Scholar, 9.Bonnar J. McNicol G.P. Douglas A.S. Coagulation and fibrinolytic mechanisms during and after normal childbirth.Br Med J. 1970; 2: 200-3Crossref PubMed Scopus (101) Google Scholar. Dilutional coagulopathy refers to replacement of blood loss with crystalloid and colloid, leading to dilution of coagulation factors and platelets. Consumption localized to the placental bed and uterus may be marked in placental abruption and may also be a feature of uterine atony and retained or adherent placenta. Disseminated intravascular coagulation (DIC) is uncommon during PPH but is associated with amniotic fluid embolus (AFE), infection and severe cases of abruption and pre‐eclampsia 7.Levi M. Pathogenesis and management of peripartum coagulopathic calamities (disseminated intravascular coagulation and amniotic fluid embolism).Thromb Res. 2013; 131: S32-4Abstract Full Text PDF PubMed Scopus (30) Google Scholar. It is unusual to develop an early coagulopathy when bleeding is caused by atony or trauma. In 244 women whose PPH was predominantly caused by atony, trauma and retained placental tissue, 98% had fibrinogen > 2 g L−1 when tested at blood loss of 1000 mL 10.Wikkelsø A.J. Edwards H.M. Afshari A. Stensballe J. Langhoff‐Roos J. Albrechtsen C. Ekelund K. Hanke G. Secher E.L. Sharif H.F. Pedersen L.M. Troelstrup A. Lauenborg J. Mitchell A.U. Fuhrmann L. Svare J. Madsen M.G. Bødker B. Møller A.M. FIB‐PPH Trial GroupPre‐emptive treatment with fibrinogen concentrate for postpartum haemorrhage: randomized controlled trial.Br J Anaesth. 2015; 114: 623-33Abstract Full Text Full Text PDF PubMed Scopus (154) Google Scholar and > 97% of 272 women with bleeds of 1000–2000 mL secondary to atony or trauma had a normal PT/aPTT and fibrinogen > 2 g L−1 (Table S1). Early coagulopathy is associated with placental abruptions and AFE 6.Collis R.E. Collins P.W. Haemostatic management of obstetric haemorrhage.Anaesthesia. 2015; 70: 78-86Crossref PubMed Google Scholar, 11.Collins P.W. Lilley G. Bruynseels D. Fibrin‐based clot formation an early and rapidly biomarker for progression of postpartum hemorrhage: a prospective study.Blood. 2014; 124: 585-95Crossref Scopus (150) Google Scholar, 12.Charbit B. Mandelbrot L. Samain E. Baron G. Haddaoui B. Keita H. Sibony O. Mahieu‐Caputo D. Hurtaud‐Roux M.F. Huisse M.G. Denninger M.H. de Prost D. PPH Study GroupThe decrease of fibrinogen is an early predictor of the severity of postpartum hemorrhage.J Thromb Haemost. 2007; 5: 266-73Crossref PubMed Scopus (501) Google Scholar (Table S1). Bleeds of any etiology that are diagnosed late or when the volume of bleeding has been underestimated may be associated with coagulopathy, highlighting the need for early recognition of PPH 4.Shields L.E. Wiesner S. Fulton J. Pelletreau B. Comprehensive maternal hemorrhage protocols reduce the use of blood products and improve patient safety.Am J Obstet Gynecol. 2015; 212: 272-80Abstract Full Text Full Text PDF PubMed Scopus (144) Google Scholar. Hemostasis may be assessed by: (i) clinical observation, (ii) laboratory‐based PT/aPPT, Clauss fibrinogen and platelet count, and (iii) point of care testing (POCT) 13.Solomon C. Collis R.E. Collins P.W. Haemostatic monitoring during postpartum haemorrhage and implications for management.Br J Anaesth. 2012; 109: 851-63Abstract Full Text Full Text PDF PubMed Scopus (149) Google Scholar. No high‐level data suggest that any strategy is better and all three may be used simultaneously. Coagulopathies may evolve rapidly and repeated testing and observation of trends is more useful than single measurements. Laboratory tests are widely available and have well‐regulated quality control 5.Allard S. Green L. Hunt B.J. How we manage the haematological aspects of major obstetric haemorrhage.Br J Haematol. 2014; 164: 177-88Crossref PubMed Scopus (39) Google Scholar, 13.Solomon C. Collis R.E. Collins P.W. Haemostatic monitoring during postpartum haemorrhage and implications for management.Br J Anaesth. 2012; 109: 851-63Abstract Full Text Full Text PDF PubMed Scopus (149) Google Scholar but are often too slow to be useful in acute and rapidly evolving bleeds and inevitably reflect past hemostatic status. Serial tests are useful, however, for following trends in an evolving clinical scenario. Clauss fibrinogen should always be measured as part of the routine coagulation screen because it falls early and may be reduced to a clinically significant level despite adequate levels of other procoagulant factors 5.Allard S. Green L. Hunt B.J. How we manage the haematological aspects of major obstetric haemorrhage.Br J Haematol. 2014; 164: 177-88Crossref PubMed Scopus (39) Google Scholar, 12.Charbit B. Mandelbrot L. Samain E. Baron G. Haddaoui B. Keita H. Sibony O. Mahieu‐Caputo D. Hurtaud‐Roux M.F. Huisse M.G. Denninger M.H. de Prost D. PPH Study GroupThe decrease of fibrinogen is an early predictor of the severity of postpartum hemorrhage.J Thromb Haemost. 2007; 5: 266-73Crossref PubMed Scopus (501) Google Scholar, 13.Solomon C. Collis R.E. Collins P.W. Haemostatic monitoring during postpartum haemorrhage and implications for management.Br J Anaesth. 2012; 109: 851-63Abstract Full Text Full Text PDF PubMed Scopus (149) Google Scholar, 14.Bell S.F. Rayment R. Collins P.W. Collis R.E. The use of fibrinogen concentrate to correct hypofibrinogenaemia rapidly during obstetric haemorrhage.Int J Obstet Anesth. 2010; 19: 218-23Abstract Full Text Full Text PDF PubMed Scopus (108) Google Scholar. Derived fibrinogen assays (indirectly measured) may be misleading and should not be used 15.Mackie I.J. Kitchen S. Machin S.J. Lowe G.D.O. Guidelines on fibrinogen assays.Br J Haematol. 2003; 121: 396-404Crossref PubMed Scopus (211) Google Scholar. DIC is uncommon in PPH and is diagnosed based on ISTH criteria 16.Levi M. Toh C.H. Thachil J. Watson H.G. Guidelines for the diagnosis and management of disseminated intravascular coagulation.Br J Haematol. 2009; 145: 24-33Crossref PubMed Scopus (767) Google Scholar, although this scoring system is not validated in the context of PPH. DIC is characterized by falling platelets and fibrinogen and rising fibrin degradation products (FDPs). FDPs are raised at term and there are no data available from which to define a cut‐off that is diagnostic of DIC during PPH 16.Levi M. Toh C.H. Thachil J. Watson H.G. Guidelines for the diagnosis and management of disseminated intravascular coagulation.Br J Haematol. 2009; 145: 24-33Crossref PubMed Scopus (767) Google Scholar. In an acute bleed it may not be possible to distinguish DIC from other causes of coagulopathy. Recognition of DIC, if possible, is important because of the potential for end‐organ microvascular thrombosis. POCTs using thromboelastometry (TEM), combined with a treatment algorithm, are associated with reduced bleed volume and blood‐product use both outside 17.Afshari A. Wikkelsø A. Brok J. Møller A.M. Wetterslev J. Thrombelastography (TEG) or thromboelastometry (ROTEM) to monitor haemotherapy versus usual care in patients with massive transfusion.Cochrane Database Syst Rev. 2011; 16: CD007871Google Scholar and within the obstetric setting 6.Collis R.E. Collins P.W. Haemostatic management of obstetric haemorrhage.Anaesthesia. 2015; 70: 78-86Crossref PubMed Google Scholar, 18.Mallaiah S. Barclay P. Harrod I. Chevannes C. Bhalla A. Introduction of an algorithm for ROTEM‐guided fibrinogen concentrate administration in major obstetric haemorrhage.Anaesthesia. 2015; 70: 166-75Crossref PubMed Scopus (125) Google Scholar. The main advantage is that results are known sooner. It is helpful to know that hemostasis is normal so that clinicians can focus on treating other causes of bleeding 6.Collis R.E. Collins P.W. Haemostatic management of obstetric haemorrhage.Anaesthesia. 2015; 70: 78-86Crossref PubMed Google Scholar. If used, a quality control protocol should be agreed with the hematology department. Normal ranges for TEM during pregnancy differ from those in the non‐pregnant population. The mean clot firmness and alpha angle (Rotem®) and maximum amplitude and alpha angle (TEG®) are larger and clot time (Rotem®) and reaction time (TEG®) are shorter; this should be taken into account when interpreting results 13.Solomon C. Collis R.E. Collins P.W. Haemostatic monitoring during postpartum haemorrhage and implications for management.Br J Anaesth. 2012; 109: 851-63Abstract Full Text Full Text PDF PubMed Scopus (149) Google Scholar, 19.De Lange N.M. Lancé M.D. de Groot R. Beckers E.A.M. Henskens Y.M. Scheepers H.C.J. Obstetric hemorrhage and coagulation: an update. Thromboelastography, thromboelastometry, and conventional coagulation tests in the diagnosis and prediction of postpartum hemorrhage.Obstet Gynecol Surv. 2012; 67: 426-35Crossref PubMed Scopus (71) Google Scholar, 20.Hill J.S. Devenie G. Powell M. Point‐of‐care testing of coagulation and fibrinolytic status during postpartum haemorrhage: developing a thrombelastography®‐guided transfusion algorithm.Anaesth Intensive Care. 2012; 40: 1007-15Crossref PubMed Google Scholar. Systemic hyperfibrinolysis can be detected by TEM but TEM lacks sensitivity in less severe cases 21.Raza I. Davenport R. Rourke C. Platton S. Manson J. Spoors C. Khan S. De'Ath H.D. Allard S. Hart D.P. Pasi K.J. Hunt B.J. Stanworth S. MacCallum P.K. Brohi K. The incidence and magnitude of fibrinolytic activation in trauma patients.J Thromb Haemost. 2013; 11: 307-14Crossref PubMed Scopus (344) Google Scholar. One expert group recommended the use of TEM for PPH (http://www.aagbi.org/sites/default/files/obstetric_anaesthetic_services_2013.pdf, accessed 26 January 2015) although another group stated that there is insufficient evidence to recommend routine use (https://www.nice.org.uk/guidance/htdg13/chapter/1-executive-summary, accessed 15 February 2015). The Fibtem® assay can be used as a surrogate measure of fibrinogen during PPH 11.Collins P.W. Lilley G. Bruynseels D. Fibrin‐based clot formation an early and rapidly biomarker for progression of postpartum hemorrhage: a prospective study.Blood. 2014; 124: 585-95Crossref Scopus (150) Google Scholar, 13.Solomon C. Collis R.E. Collins P.W. Haemostatic monitoring during postpartum haemorrhage and implications for management.Br J Anaesth. 2012; 109: 851-63Abstract Full Text Full Text PDF PubMed Scopus (149) Google Scholar, 22.Huissoud C. Carrabin N. Audibert F. Levrat A. Massignon D. Berland M. Rudigoz R.C. Bedside assessment of fibrinogen level in postpartum haemorrhage by thrombelastometry.BJOG. 2009; 116: 1097-102Crossref PubMed Scopus (183) Google Scholar, 23.van Rheenen‐Flach L.E. Zweegman S. Boersma F. Lenglet J.E. Twisk J.W.R. Bolte A.C. A prospective longitudinal study on rotation thromboelastometry in women with uncomplicated pregnancies and postpartum.Aust N Z J Obstet Gynaecol. 2013; 53: 32-6Crossref PubMed Scopus (26) Google Scholar. This assay does not measure the same hemostatic parameter as Clauss fibrinogen but provides a similar indication of hemostatic competence and outcome 11.Collins P.W. Lilley G. Bruynseels D. Fibrin‐based clot formation an early and rapidly biomarker for progression of postpartum hemorrhage: a prospective study.Blood. 2014; 124: 585-95Crossref Scopus (150) Google Scholar. Algorithms using Rotem and TEG during PPH have been published 6.Collis R.E. Collins P.W. Haemostatic management of obstetric haemorrhage.Anaesthesia. 2015; 70: 78-86Crossref PubMed Google Scholar, 18.Mallaiah S. Barclay P. Harrod I. Chevannes C. Bhalla A. Introduction of an algorithm for ROTEM‐guided fibrinogen concentrate administration in major obstetric haemorrhage.Anaesthesia. 2015; 70: 166-75Crossref PubMed Scopus (125) Google Scholar, 24.Pavord S. Maybury H. How I treat postpartum hemorrhage.Blood. 2015; 125: 2759-70Crossref PubMed Scopus (33) Google Scholar.•We recommend monitoring hemostasis with either PT/aPTT and Clauss fibrinogen or POCTs using thromboelastometry during PPH. If bleeding persists serial measures should be performed.•If thromboelastometry is used, blood component replacement should be based on a local algorithm and a quality control protocol agreed with hematology.•We recommend laboratory monitoring of platelet count.•We recommend that derived fibrinogen assays (indirectly measured) should not be used. There are limited data available to inform the treatment of hemostatic impairment during PPH. It is not known whether it is best to correct to normality for the time of delivery or to normality for the non‐pregnant population. Fibrinogen falls earlier than other coagulation factors during PPH and may be low despite normal PT/aPTT 5.Allard S. Green L. Hunt B.J. How we manage the haematological aspects of major obstetric haemorrhage.Br J Haematol. 2014; 164: 177-88Crossref PubMed Scopus (39) Google Scholar, 12.Charbit B. Mandelbrot L. Samain E. Baron G. Haddaoui B. Keita H. Sibony O. Mahieu‐Caputo D. Hurtaud‐Roux M.F. Huisse M.G. Denninger M.H. de Prost D. PPH Study GroupThe decrease of fibrinogen is an early predictor of the severity of postpartum hemorrhage.J Thromb Haemost. 2007; 5: 266-73Crossref PubMed Scopus (501) Google Scholar, 25.De Lloyd L. Bovington R. Kaye A. Collis R.E. Rayment R. Sanders J. Rees A. Collins P.W. Standard haemostatic tests following major obstetric haemorrhage.Int J Obstet Anesth. 2011; 20: 135-41Abstract Full Text Full Text PDF PubMed Scopus (137) Google Scholar, 26.Stainsby D. MacLennan S. Thomas D. Isaac J. Hamilton P.J. Guidelines on the management of massive blood loss.Br J Haematol. 2006; 135: 634-41Crossref PubMed Scopus (322) Google Scholar. Observational studies suggest that fibrinogen of 1–1.5 g L−1 is too low for adequate hemostasis during ongoing PPH. Fibrinogen < 3 and especially < 2 g L−1 is associated with progression of bleeding, increased red blood cell (RBC) and blood component requirement and the need for invasive procedures. Fibrinogen > 4 g L−1 is associated with a low rate of progression to severe PPH 11.Collins P.W. Lilley G. Bruynseels D. Fibrin‐based clot formation an early and rapidly biomarker for progression of postpartum hemorrhage: a prospective study.Blood. 2014; 124: 585-95Crossref Scopus (150) Google Scholar, 12.Charbit B. Mandelbrot L. Samain E. Baron G. Haddaoui B. Keita H. Sibony O. Mahieu‐Caputo D. Hurtaud‐Roux M.F. Huisse M.G. Denninger M.H. de Prost D. PPH Study GroupThe decrease of fibrinogen is an early predictor of the severity of postpartum hemorrhage.J Thromb Haemost. 2007; 5: 266-73Crossref PubMed Scopus (501) Google Scholar, 27.Cortet M. Deneux‐Tharaux C. Dupont C. Colin C. Rudigoz R.C. Bouvier‐Colle M.H. Huissoud C. Association between fibrinogen level and severity of postpartum haemorrhage: secondary analysis of a prospective trial.Br J Anaesth. 2012; 108: 984-9Abstract Full Text Full Text PDF PubMed Scopus (175) Google Scholar, 28.De Lloyd L. Collins P.W. Kaye A. Collis R.E. Early fibrinogen as a predictor of red cell requirements during postpartum haemorrhage.Int J Obstet Anesth. 2012; 21: S13Google Scholar, 29.Gayat E. Resche‐Rigon M. Morel O. Rossignol M. Mantz J. Nicolas‐Robin A. Nathan‐Denizot N. Lefrant J.Y. Mercier F.J. Samain E. Fargeaudou Y. Barranger E. Laisné M.J. Bréchat P.H. Luton D. Ouanounou I. Plaza P.A. Broche C. Payen D. Mebazaa A. Predictive factors of advanced interventional procedures in a multicentre severe postpartum haemorrhage study.Intensive Care Med. 2011; 37: 1816-25Crossref PubMed Scopus (93) Google Scholar, 30.Kenyon S. Intrapartum care: care of healthy women and their babies during childbirth. http://www.nice.org.uk/guidance/cg55/chapter/guidance 2007. Accessed 16 November 2015.Google Scholar. A double‐blind randomized controlled trial has shown that pre‐emptive infusion of 2 g fibrinogen concentrate in women with 500–1000 mL PPH has no benefit; however, the mean fibrinogen at the time of randomization was > 4 g L−1 and this is a likely explanation for the lack of efficacy 10.Wikkelsø A.J. Edwards H.M. Afshari A. Stensballe J. Langhoff‐Roos J. Albrechtsen C. Ekelund K. Hanke G. Secher E.L. Sharif H.F. Pedersen L.M. Troelstrup A. Lauenborg J. Mitchell A.U. Fuhrmann L. Svare J. Madsen M.G. Bødker B. Møller A.M. FIB‐PPH Trial GroupPre‐emptive treatment with fibrinogen concentrate for postpartum haemorrhage: randomized controlled trial.Br J Anaesth. 2015; 114: 623-33Abstract Full Text Full Text PDF PubMed Scopus (154) Google Scholar. Fibrinogen can be replaced using cryoprecipitate or fibrinogen concentrate 31.Ahmed S. Harrity C. Johnson S. Varadkar S. McMorrow S. Fanning R. Flynn C.M. O'Riordan J.M. Byrne B.M. The efficacy of fibrinogen concentrate compared with cryoprecipitate in major obstetric haemorrhage ‐ an observational study.Transfus Med. 2012; 22: 344-9Crossref PubMed Scopus (82) Google Scholar. Fibrinogen concentrate is not licensed for PPH in all countries and cryoprecipitate is unavailable in others. The dose should be calculated based on the measured and target fibrinogen. Two pools of cryoprecipitate would be expected to increase fibrinogen by about 1 g L−1 in the average woman, although this will vary depending on consumption. Fibrinogen concentrate rapidly corrects severe hypofibrinogenemia during PPH and studies report improved clinical hemostasis 14.Bell S.F. Rayment R. Collins P.W. Collis R.E. The use of fibrinogen concentrate to correct hypofibrinogenaemia rapidly during obstetric haemorrhage.Int J Obstet Anesth. 2010; 19: 218-23Abstract Full Text Full Text PDF PubMed Scopus (108) Google Scholar, 31.Ahmed S. Harrity C. Johnson S. Varadkar S. McMorrow S. Fanning R. Flynn C.M. O'Riordan J.M. Byrne B.M. The efficacy of fibrinogen concentrate compared with cryoprecipitate in major obstetric haemorrhage ‐ an observational study.Transfus Med. 2012; 22: 344-9Crossref PubMed Scopus (82) Google Scholar, 32.Glover N.J. Collis R.E. Collins P. Fibrinogen concentrate use during major obstetric haemorrhage.Anaesthesia. 2010; 65: 1229-30Crossref PubMed Scopus (29) Google Scholar, 33.Gollop N.D. Chilcott J. Benton A. Rayment R. Jones J. Collins P.W. National audit of the use of fibrinogen concentrate to correct hypofibrinogenaemia.Transfus Med. 2012; 22: 350-5Crossref PubMed Scopus (21) Google Scholar, 34.Weinkove R. Rangarajan S. Fibrinogen concentrate for acquired hypofibrinogenaemic states.Transfus Med. 2008; 18: 151-7Crossref PubMed Scopus (102) Google Scholar. Increasing fibrinogen by 1 g L−1 requires about 60 mg kg−1 fibrinogen concentrate 33.Gollop N.D. Chilcott J. Benton A. Rayment R. Jones J. Collins P.W. National audit of the use of fibrinogen concentrate to correct hypofibrinogenaemia.Transfus Med. 2012; 22: 350-5Crossref PubMed Scopus (21) Google Scholar. In an observational study, fibrinogen concentrate was infused if the Fibtem A5 was < 7 mm (and considered if < 12 mm in severe bleeds). This significantly reduced the use of RBC and fresh frozen plasma (FFP) (> 75% of women received no FFP) compared with the use of shock packs and also resulted in fewer women requiring > 6 units RBC and reduced transfusion‐associated circulatory overload (TACO) and ITU admissions 18.Mallaiah S. Barclay P. Harrod I. Chevannes C. Bhalla A. Introduction of an algorithm for ROTEM‐guided fibrinogen concentrate administration in major obstetric haemorrhage.Anaesthesia. 2015; 70: 166-75Crossref PubMed Scopus (125) Google Scholar, 35.Mallaiah S. Chevannes C. McNamara H. Barclay P. A reply.Anaesthesia. 2015; 70: 760-1Crossref PubMed Scopus (16) Google Scholar. There are currently three prospective randomized studies investigating the role of fibrinogen concentrate in PPH (NCT02155725, NCT01910675 and ISRCTN46295339). The appropriate fibrinogen intervention trigger or target level is unknown. A pragmatic view, pending results of ongoing trials, is that during ongoing PPH a fibrinogen level of at least 2 g L−1 (Fibtem A5 about 12 mm) should be maintained even if PT/aPTT are normal. In cases of severe abruption and AFE some groups suggest considering the empirical infusion of two pools of cryoprecipiate 4.Shields L.E. Wiesner S. Fulton J. Pelletreau B. Comprehensive maternal hemorrhage protocols reduce the use of blood products and improve patient safety.Am J Obstet Gynecol. 2015; 212: 272-80Abstract Full Text Full Text PDF PubMed Scopus (144) Google Scholar. There is no benefit of increasing the fibrinogen level above 4 g L−1 10.Wikkelsø A.J. Edwards H.M. Afshari A. Stensballe J. Langhoff‐Roos J. Albrechtsen C. Ekelund K. Hanke G. Secher E.L. Sharif H.F. Pedersen L.M. Troelstrup A. Lauenborg J. Mitchell A.U. Fuhrmann L. Svare J. Madsen M.G. Bødker B. Møller A.M. FIB‐PPH Trial GroupPre‐emptive treatment with fibrinogen concentrate for postpartum haemorrhage: randomized controlled trial.Br J Anaesth. 2015; 114: 623-33Abstract Full Text Full Text PDF PubMed Scopus (154) Google Scholar. Fixed‐ratio protocols such as 1 : 1, 3 : 2 or 6 : 4 RBC : FFP, based on data derived from trauma cases, have been advocated for PPH 3.Royal College of Obstetricians and Gynaecologists. Prevention and management of postpartum haemorrhage. Green‐top guideline No. 52, 2009. http://www.rcog.org.uk/files/rcog-corp/GT52PostpartumHaemorrhage0411.pdf 2013. Accessed 16 November 2015.Google Scholar, 4.Shields L.E. Wiesner S. Fulton J. Pelletreau B. Comprehensive maternal hemorrhage protocols reduce the use of blood products and improve patient safety.Am J Obstet Gynecol. 2015; 212: 272-80Abstract Full Text Full Text PDF PubMed Scopus (144) Google Scholar, 36.Pasquier P. Gayat E. Rackelboom T. La Rosa J. Tashkandi A. Tesniere A. Ravinet J. Vincent J.L. Tsatsaris V. Ozier Y. Goffinet F. Mignon A. An observational study of the fresh frozen plasma: red blood cell ratio in postpartum hemorrhage.Anesth Analg. 2013; 116: 155-61Crossref PubMed Scopus (42) Google Scholar, 37.Shields L.E. Smalarz K. Reffigee L. Mugg S. Burdumy T.J. Propst M. Comprehensive maternal hemorrhage protocols improve patient safety and reduce utilization of blood products.Am J Obstet Gynecol. 2011; 205: 368Abstract Full Text Full Text PDF PubMed Scopus (113) Google Scholar (https://www.cmqcc.org/ob_hemorrhage accessed 27/Jan/2015). There is no high‐quality evidence supporting that this approach alters outcomes in PPH but it may reduce the proportion of women progressing to severe hemostatic impairment 37.Shields L.E. Smalarz K. Reffigee L. Mugg S. Burdumy T.J. Propst M. Comprehensive maternal hemorrhage protocols improve patient safety and reduce utilization of blood products.Am J Obstet Gynecol. 2011; 205: 368Abstract Full Text Full Text PDF PubMed Scopus (113) Google Scholar. Drawbacks of early, unmonitored FFP are that the majority of women have normal coagulation at the time of administration 10.Wikkelsø A.J. Edwards H.M. Afshari A. Stensballe J. Langhoff‐Roos J. Albrechtsen C. Ekelund K. Hanke G. Secher E.L. Sharif H.F. Pedersen L.M. Troelstrup A. Lauenborg J. Mitchell A.U. Fuhrmann L. Svare J. Madsen M.G. Bødker B. Møller A.M. FIB‐PPH Trial GroupPre‐emptive treatment with fibrinogen concentrate for postpartum haemorrhage: randomized controlled trial.Br J Anaesth. 2015; 114: 623-33Abstract Full Text Full Text PDF PubMed Scopus (154) Google Scholar, 11.Collins P.W. Lilley G. Bruynseels D. Fibrin‐based clot formation an early and rapidly biomarker for progression of postpartum hemorrhage: a prospective study.Blood. 2014; 124: 585-95Crossref Scopus (150) Google Scholar, 12.Charbit B. Mandelbrot L. Samain E. Baron G. Haddaoui B. Keita H. Sibony O. Mahieu‐Caputo D. Hurtaud‐Roux M.F. Huisse M.G. Denninger M.H. de Prost D. PPH Study GroupThe decrease of fibrinogen is an early predictor of the severity of postpartum hemorrhage.J Thromb Haemost. 2007; 5: 266-73Crossref PubMed Scopus (501) Google Scholar, 25.De Lloyd L. Bovington R. Kaye A. Collis R.E. Rayment R. Sanders J. Rees A. Collins P.W. Standard haemostatic tests following major obstetric haemorrhage.Int J Obstet Anesth. 2011; 20: 135-41Abstract Full Text Full Text PDF PubMed Scopus (137) Google Scholar and its association with TACO 18.Mallaiah S. Barclay P. Harrod I. Chevannes C. Bhalla A. Introduction of an algorithm for ROTEM‐guided fibrinogen concentrate administration in major obstetric haemorrhage.Anaesthesia. 2015; 70: 166-75Crossref PubMed Scopus (125) Google Scholar and transfusion‐related acute lung injury (TRALI) 38.Teofili L. Bianchi M. Zanfini B.A. Catarci S. Sicuranza R. Spartano S. Zini G. Draisci G. Acute lung injury complicating blood transfusion in post‐partum hemorrhage: Incidence and risk factors.Mediterr J Hematol Infect Dis. 2014; 6: e2014069Crossref PubMed Scopus (16) Google Scholar. Early FFP will usually result in women being infused with blood products with lower concentrations of fibrinogen and other coagulation factors (FVIII and von Willebrand factor) than they have circulating because FFP has a fibrinogen level of around 2–2.5 g L−1 compared with an average fibrinogen of 4–4.5 g L−1 at the time of moderate/severe PPH 10.Wikkelsø A.J. Edwards H.M. Afshari A. Stensballe J. Langhoff‐Roos J. Albrechtsen C. Ekelund K. Hanke G. Secher E.L. Sharif H.F. Pedersen L.M. Troelstrup A. Lauenborg J. Mitchell A.U. Fuhrmann L. Svare J. Madsen M.G. Bødker B. Møller A.M. 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