Combined life-threatening thromboses and hemorrhages in a patient with afibrinogenemia and antithrombin deficiency.

BACKGROUND: Patients with congenital afibrinogenemia suffer from spontaneous recurrent severe bleeding. While fibrinogen concentrates are known to effectively treat bleeding episodes, thrombotic complications often occur upon replacement therapy, rendering clinical management highly challenging. CASE PRESENTATION: We hereby report a case of combined afibrinogenemia and congenital antithrombin deficiency manifested by recurrent life-threatening bleeding, as well as spontaneous severe arterial occlusion, such as acute coronary syndrome and stroke, and venous thromboses like pulmonary embolism.Secondary fibrinogen prophylaxis is recommended following any initial life-threatening bleeding episode in patients with afibrinogenemia, yet the high associated risk of thrombosis illustrates the complexity of choosing the most effective prophylaxis strategy combining fibrinogen concentrate with antithrombotic agent for optimal protection against the risk of both severe bleeding and thrombosis. For our patient, the thrombin generation assay objectively confirmed her prothrombotic tendency. CONCLUSION: This case may help us better understand the pathophysiology of arterial thrombosis in afibrinogenemia, while highlighting the difficulty of managing such complications.

A single-centre study of haemostatic outcomes of joint replacement in von Willebrand disease and control patients and an analysis of the literature.

INTRODUCTION: Haemostatic assessments of patients with von Willebrand disease (VWD) who undergo total knee arthroplasty (TKA) and total hip arthroplasty (THA) have mainly relied on subjective parameters. AIMS: To compare objective haemostatic outcomes of TKA/THA in VWD patients and controls without bleeding disorders. METHODS: We retrospectively analysed haemostatic outcomes in VWD patients undergoing TKA/THA from 1993 to 2011 and compared them with two matched controls per operation. Using one-way analysis of variance, we tested the effect of VWD on bleeding risk after TKA and THA. RESULTS: Twelve VWD patients (6 type 1, 3 type 2M, 1 each of types 2A/2B/3) undergoing 19 operations (12 TKA, 7 THA) were matched to 38 controls. One (5%) of 19 operations in VWD patients and none of the control operations met clinical criteria for major bleeding. Baseline and postoperative day 1 haemoglobin levels, postoperative blood loss, transfused red blood cells (RBCs) and mean hospitalization days were not significantly different. More VWD patients than controls received RBC transfusions [12 (63%) vs. 12 (32%)]. Only 9 (47%) VWD patients vs. 38 (100%) controls received pharmacologic VTE prophylaxis. No postoperative symptomatic VTE occurred in either group. CONCLUSION: In this largest, single-institutional study, von Willebrand factor replacement based on daily levels resulted in low frequency of major bleeding in VWD patients after TKA/THA. RBC transfusion was more frequent compared with matched controls, but other objective measures of haemostasis were similar. Lack of sufficient details in published reports precluded comparison of haemostatic outcomes.

Perioperative management and neuraxial analgesia in women with factor XI deficiency (<60 IU/dL): a French multicenter observational study of 314 pregnancies.

Background: Factor (F)XI deficiency is a rare bleeding disorder with a poor correlation between bleeding tendency and FXI level. Management of pregnant women with FXI deficiency is not clearly established, especially regarding neuraxial analgesia (NA). Objectives: A retrospective multicenter observational study was conducted in French hemostasis centers on pregnant women with FXI of <60 IU/dL. Methods: Data to report were (i) FXI levels before pregnancy and at time of delivery, (ii) type of NA and delivery management modalities, and (iii) possible complications related to NA and bleeding complications. Results: Three hundred fourteen pregnancies in patients with FXI deficiency of <60 IU/dL were reported (from 20 centers); among them, 199 NA procedures have been completed (137 epidurals and 61 spinals, 1 had both). The period of childbirth was mostly from 2014 to 2020 (281/314; 89.5%). Congenital FXI deficiency was established with certainty by investigators in 32.8% patients (n = 103). Previous bleedings were described in 20.4% of the patients (64/314; 45.3% cutaneous, 31.3% gynecologic, and 15.6% postsurgical). Thirteen deliveries had an NA procedure with FXI of <30 IU/dL, 42 with FXI of 30-40 IU/dL, and 118 with FXI of 40-60 IU/dL. Median FXI levels at delivery in the epidural and spinal groups were not significantly different but were significantly lower in the group without NA by medical staff contraindications. There were no complications related to NA. A 17.5% postpartum hemorrhage or excessive postpartum bleeding incidence was reported, which is consistent with previous data. Conclusion: Our data support the use of a 30 IU/dL FXI threshold for NA, as suggested by the French proposals published in August 2023.

Thrombin generation in patients with factor XI deficiency and clinical bleeding risk.

SUMMARY: Factor XI (FXI) deficiency is a rare bleeding disorder. Most patients with FXI deficiency are mild bleeders but certain patients with similar FXI activity exhibit different bleeding phenotype. Routine laboratory assays do not help physicians to estimate the individual bleeding risk in these patients. Thrombin generation test (TGT) is a more comprehensive, global function test of the clotting system. We investigated whether or not the bleeding tendency of patients with FXI deficiency is correlated with features of the TGT. Twenty-four patients with FXI deficiency were divided in two groups: (i) severe bleeders (n = 9) and (ii) mild or non-bleeders (n = 15). All severe bleeders had a personal history of surgery-related severe bleeding. Thrombin generation (TG) was measured in platelet-rich plasma (PRP) using a low concentration of tissue factor 0.5 pm. In patients exhibiting severe bleeding tendency, independently of their FXI level, a dramatically impaired TG was observed. For example, despite a low plasma FXI = 1 IU dl(-1), a clinically non-bleeding individual exhibited normal TG results whereas another patient with severe bleeding history and FXI = 40 IU dl(-1) had a very low TG capacity. Low velocity and delayed TG were the main parameters suggesting a higher bleeding risk. DNA analysis of patients reported eight novel mutations of the FXI gene but neither mutation location nor secretion or not of the variant correlated with the bleeding tendency. The results of this study suggest that TG measurement in PRP may be a useful tool to predict bleeding risk in FXI deficiency and should be studied further in larger prospective clinical studies.

Evaluation of rotation thrombelastography for the diagnosis of hyperfibrinolysis in trauma patients.

BACKGROUND: Blood loss and uncontrollable bleeding are major factors affecting survival in trauma patients. Because treatment with antifibrinolytic drugs may be effective, early detection of hyperfibrinolysis with rotation thrombelastography (ROTEM may be beneficial. METHODS: Eighty-seven trauma patients were included in this prospective observational study. Blood samples were collected at admission. After in vitro activation with tissue factor (EXTEM) and inhibition with aprotinin (APTEM), ROTEM parameters including maximal clot firmness (MCF) and clot lysis index at 30 min (CLI(30)) were determined. Hyperfibrinolysis was defined as a euglobulin lysis time (ELT) <90 min. Threshold for ROTEM parameters were determined with receiver-operating characteristic curves (ROC) analysis according to the ELT results. RESULTS: ELT was determined in a subgroup of 23 patients. In this group of patients, ROC analysis showed that for a threshold of 18 mm (MCF-EXTEM), 71% (CLI(30)) and 7% (increase of MCF-APTEM), sensitivity was, respectively, 100%, 75%, and 80% with a specificity of 100%. With the application of these thresholds to the whole trauma cohort, ROTEM analysis detected hyperfibrinolysis in five patients [6%, 95% confidence interval (CI): 2-13%]. As expected, patients with hyperfibrinolysis were more severely injured (median Injury Severity Score: 75 vs 20, P<0.05), had greater coagulation abnormalities [international normalized ratio (INR): 8.2 vs 1.3, P<0.05; fibrinogen: 0.0 vs 2.2 g litre(-1), P<0.05], and a higher mortality rate (100%, CI: 48-100% vs 11% CI: 5-20%, P<0.05). CONCLUSIONS: ROTEM provided rapid and accurate detection of hyperfibrinolysis in severely injured trauma patients.

Comparison of an automated chemiluminescent assay to a manual ELISA assay for determination of von Willebrand Factor collagen binding activity on VWD plasma patients previously diagnosed through molecular analysis of VWF.

INTRODUCTION: The correct diagnosis and classification of VWD (von Willebrand disease) is crucial and must be optimized by including the collagen binding assay (VWF:CB). VWF:CB remains an under-recognized tool, not fully automated. The objective of this study was to evaluate and to compare the previously evaluated automated chemiluminescent assay (HemosIL AcuStar VWF:CB) to the ELISA ASSERACHROM® assay used routinely in our laboratory in patients with molecular diagnosis of VWD. METHODS: A plasma sample from 49 patients previously diagnosed with VWD (type 1; type 2A, type 2M, type 2B) through phenotype and VWF (von Willebrand factor) analysis and 15 healthy controls was analysed. The VWF ristocetin cofactor activity (VWF:Rco) and VWF antigen (VWF:Ag) were performed simultaneously on the VWD plasma samples, and VWF:CB/VWF:Ag ratios were calculated. RESULTS: The AcuStar VWF:CB assay was quickly performed with Pearson's correlation coefficient (r²) of .9571 between assays and a bias of +5.1U/dL (AcuStar > ELISA). Discrepancies of VWF:CB/VWF:Ag ratio were observed in type 2M-2A-like VWD (ratio <0.6 with AcuStar assay in 4/5 samples). CONCLUSION: The AcuStar VWF:CB assay has demonstrated good performance to detect VWF mutational changes with capacity to discriminate quickly principal types of VWD.

Diagnosis of early coagulation abnormalities in trauma patients by rotation thrombelastography.

BACKGROUND: Reagent-supported thromboelastometry with the rotation thrombelastography (e.g. ROTEM) is a whole blood assay that evaluates the visco-elastic properties during blood clot formation and clot lysis. A hemostatic monitor capable of rapid and accurate detection of clinical coagulopathy within the resuscitation room could improve management of bleeding after trauma. OBJECTIVES: The goals of this study were to establish whether ROTEM correlated with standard coagulation parameters to rapidly detect bleeding disorders and whether it can help to guide transfusion. METHODS: Ninety trauma patients were included in the study. At admission, standard coagulation assays were performed and ROTEM parameters such as clot formation time (CFT) and clot amplitude (CA) were obtained at 15 min (CA(15)) with two activated tests (INTEM, EXTEM) and at 10 min (CA(10)) with a test analyzing specifically the fibrin component of coagulation (FIBTEM). RESULTS: Trauma induced significant modifications of coagulation as assessed by standard assays and ROTEM. A significant correlation was found between prothrombin time (PT) and CA(15)-EXTEM (r = 0.66, P < 0.0001), between activated partial thromboplastin time and CFT-INTEM (r = 0.91, P < 0.0001), between fibrinogen level and CA(10)-FIBTEM (r = 0.85, P < 0.0001), and between platelet count and CA(15)-INTEM (r = 0.57, P < 0.0001). A cutoff value of CA(15)-EXTEM at 32 mm and CA(10)-FIBTEM at 5 mm presented a good sensitivity (87% and 91%) and specificity (100% and 85%) to detect a PT > 1.5 of control value and a fibrinogen less than 1 g L(-1), respectively. CONCLUSIONS: ROTEM is a point-of-care device that rapidly detects systemic changes of in vivo coagulation in trauma patients, and it might be a helpful device in guiding transfusion.

Personalized thromboprophylaxis using a risk score for the management of pregnancies with high risk of thrombosis: a prospective clinical study.

Essentials Pregnancy is a risk factor for thrombosis. Management of thrombosis risk in pregnancy remains a challenge. Prophylaxis needs to be personalized. Our score may be a helpful tool for the management of pregnancies at high risk of thrombosis. SUMMARY: Background Patients with thrombophilia and/or a history of venous thromboembolism (VTE) are at risk of thrombosis during pregnancy. A risk score for pregnancies with an increased risk of VTE was previously described by our group (Lyon VTE score). Objectives The aim of this prospective study was to assess the efficacy and safety of our score-based prophylaxis strategy in 542 pregnancies managed between 2005 and 2015 in Lyon University Hospitals. Patients/Methods Of 445 patients included in the study, 36 had several pregnancies during the study period. Among these 445 patients, 279 had a personal history of VTE (62.7%), 299 patients (67.2%) had a thrombophilia marker, and 131 (29.4%) thrombophilic women had a personal history of VTE. During pregnancy, patients were assigned to one of three prophylaxis strategies according to the risk scoring system. Results In the antepartum period, low molecular weight heparin (LMWH) prophylaxis was prescribed to 64.5% of patients at high risk of VTE. Among them, 34.4% were treated in the third trimester only, and 30.1% were treated throughout pregnancy. During the postpartum period, all patients received LMWH for at least 6 weeks. Two antepartum-related VTEs (0.37%; one with a score of < 3 and the other with a score of > 6) and four postpartum-related VTEs (0.73%; three with scores of 3-5 and one with a score of > 6) occurred. No case of pulmonary embolism was observed during the study period. The rate of bleeding was 0.37%. No serious bleeding requiring transfusions or surgery occurred during the study period. Conclusion The use of a risk score may provide a rational decision process to implement safe and effective antepartum thromboprophylaxis in pregnant women at high risk of VTE.

Basic fibroblast growth factor increases tissue factor expression in circulating monocytes and in vascular wall.

BACKGROUND: Basic fibroblast growth factor (bFGF) promotes vascular repair and angiogenesis and can induce in vitro tissue factor (TF), a potent agent initiating thrombogenesis, which probably plays a role in angiogenesis. We investigated whether bFGF administration induced TF expression by monocytes and vascular cells. METHODS AND RESULTS: We studied TF expression in normally fed (n=16) and cholesterol-fed (2% for 6 weeks, n=16) rabbits. Animals were then randomized to receive intravenous bFGF (2.5 microg twice weekly for 3 weeks) or saline injections. TF expression was evaluated in mononuclear cells from arterial blood and in aortic sections by an immunohistochemical assay using a monoclonal anti-rabbit TF antibody (activator protein 1). Monocyte TF expression was increased by bFGF administration in both normal and hypercholesterolemic rabbits (129+/-45 versus 19+/-3 mU TF/1000 monocytes, P<0.05, and 31+/-12 versus 7+/-1 mU TF/1000 monocytes, P<0.005, respectively) and was further increased by stimulation of monocytes by endotoxin in vitro. TF expression was lower in hypercholesterolemic rabbits than in normal rabbits. In the media of the vascular wall, bFGF induced strong TF expression in normal rabbits and only weak TF expression in hypercholesterolemic ones. CONCLUSIONS: This study demonstrates that systemic administration of bFGF induces an impressive increase of TF expression in circulating monocytes and in the vascular wall in normal and to a lower extent in hypercholesterolemic rabbits. The significance of this observation in terms of inducing thrombosis in vivo needs clarification.

Management of pregnant women with increased risk of venous thrombosis.

OBJECTIVE: To evaluate the usefulness of score based management of pregnancies with high risk of venous thromboembolism (VTE). METHOD: 116 consecutive pregnancies in 109 women with confirmed thrombophilia and/or history of VTE were studied. Patients were managed in accordance with international recommendations. Recently, a VTE risk prediction score was established. An independent group assessed retrospectively and in a blinded way the usefulness of this score. RESULTS: Of the 116 pregnancies, an antithrombotic prophylaxis by low molecular weight heparin was prescribed in 61 cases (52.6%). All patients with a positive score (n=57, 49.1%) have been treated with an antenatal thromboprophylaxis. In the population where the score was negative (n=55 cases), none of the patients received antenatal prophylaxis. But, despite a negative score, four patients were treated by their general practitioner. During the study period, there was only one episode of VTE. CONCLUSION: Implementing this scoring system has resulted in favorable outcomes and a low risk of recurrent thrombosis in this limited series of women with increased risk of VTE.

Prospective evaluation of automatized PF4/heparin immunoassays HemosIL HIT-ab (PF4-H) for the diagnosis of heparin-induced thrombocytopenia.

INTRODUCTION: Recently, rapid immunoassays have been developed to allow the detection of antibodies anti-PF4/heparin. In this prospective study, we evaluated the performances of a automatized immunoassay (HemosIL HIT-Ab) in comparison with an ELISA (Zymutest HIA IgG) used for the diagnosis of heparin-induced thrombocytopenia (HIT) in association with the 4T's score. METHODS: According to the 4T's score, samples with score ≤3 had no further analysis. Two immunological assays Zymutest HIA IgG and HemosIL HIT-Ab were performed in samples with score ≥4. In patients with at least one positive immunological assay or two negative immunological assays but with high-pretest probability (4T's score ≥6), HIT was screened by one functional assay using washed platelets. RESULTS: The sensitivities of both assays were excellent and comparable (100%). The specificity was 92.3% for ELISA and 91.2% for HemosIL HIT-Ab. The analysis of the operating characteristics showed that both assays have almost identical ROCs (AUROC, 0.9951 and 0.9853, respectively, for ELISA and HemosIL HIT-Ab) and the calculating of the κ coefficient revealed a good agreement (0.67). CONCLUSION: Performance characteristics of the HemosIL HIT-Ab are comparable to the Zymutest HIA IgG. The HemosIL HIT-Ab can be used in association with the 4T's score to rule out HIT.

Factor VII, tissue factor pathway inhibitor, and monocyte tissue factor in diabetes mellitus: influence of type of diabetes, obesity index, and age.

Changes of the tissue factor (TF) pathway of blood coagulation have been described in diabetes and could be involved in its vascular complications. In order to evaluate the influence of the type of diabetes and of the obesity index and age on these changes, factor VII coagulant activity, factor VII antigen, activated factor VII, monocyte TF expression, and plasma Tissue Factor Pathway Inhibitor (TFPI) were examined in 18 Type 1 and 16 Type 2 diabetic patients compared to non-diabetic control subjects matched for age, sex, and obesity index (Types 1 and 2 controls, respectively). Multicomplicated patients were excluded. FVIIc, FVIIAg, and FVIIa were higher in Type 2 diabetic patients and controls than in Type 1 diabetic patients and controls (P< .03). However, FVIIc and FVIIAg were lower in diabetic patients than in their matched controls (P< .03). Monocyte expression of TF was not different between Types 1 and 2 diabetic patients and their matched controls except for LPS-stimulated monocyte TF activity which was lower in Type 2 diabetic patients than in Type 2 controls (P< .05). Plasma TFPI was slightly but significantly higher in Type 1 diabetic patients than in Type 1 controls (P= .01) and was correlated to glycemia. However, both in Type 2 diabetic patients and controls, TFPI was higher than in Type 1 controls and was correlated with BMI (P< .0003). These results indicate that in not multicomplicated patients, the increase of FVII and TFPI was highly dependent on obesity index and age rather than on diabetes by itself.

Monocyte tissue factor response is decreased in patients with hyperlipidemia.

Monocytes are potent regulators of blood coagulation through the expression of tissue factor (TF) on stimulation and of tissue factor pathway inhibitor (TFPI), a selective inhibitor of TF pathway. As hyperlipidemia can modify some monocyte functions, we compared the TF and TFPI expression by circulating monocytes and the plasma TFPI levels between 65 healthy normolipemic controls and 38 nontreated hyperlipemic patients. TF and TFPI relationships with plasma lipoproteins are also examined. TF and TFPI expression were evaluated in peripheral mononuclear cells after isolation from blood by density gradient centrifugation and after short culture with or without lipopolysaccharide (LPS). TF and TFPI activity and antigen were measured in mononuclear cell lysates using amidolytic assay and enzyme-linked immunosorbent assay, respectively. TFPI activity and antigen were measured in plasma using the same methods. Plasma factor VII (FVII) activity and antigen were also determined. LPS-stimulated monocyte TF activity and antigen were lower in hyperlipidemic patients than in controls (0.0001

[Impact of a quality approach for transfusion safety on prescription, circuit optimization, traceability]. / Impact d'une démarche qualité en sécurité transfusionnelle sur la prescription, l'optimisation des circuits, la traçabilité. Expérience du CHRU de Lille.

The Quality Assessment Program undertaken at the Regional University Hospital of Lille benefits from previous experience making management of this project possible: continuing education, preliminary initiation into the quality approach, and existing reference systems. The aims are to master the rates of outdated and no longer efficient red cell concentrates, to control red cell concentrate delivery time, to validate the refrigeration line integrity and to ensure a flawless marking out process. The process studied is transverse, with those taking part in it belonging to several professional categories. The method will consist in a process identification, its description and characterization according to FMECA (Failure Mode Effects and Criticality Analysis), the creation of a new process and its improvement. Thus failures should be identified and classified hierachically. The corrective actions will consist in communication aids, an education program, blood product transport and blood depot reorganization, data processing improvement and medical equipment acquisition. Quality indicators are developed according to the objectives of the study, and progress indicators are developed as a periodical assessment of blood transfusion practice. This ambitious project relies on the involvement of Hospital Management and referent network. These referents facilitate the improvement processes for those taking part in this process.

[Constitutional thrombophilias: indications of the biological profile and therapeutic consequences]. / Thrombophilies constitutionnelles: indications du bilan biologique et conséquences thérapeutiques.

In laboratory screening in patients with clinical thrombophilia (early thromboembolism episode < 50 years, spontaneous thrombosis, recurrent thrombosis, unusual site of thrombosis, thrombotic family history or coumarin-induced skin necrosis complication), an isolated or combined inherited thrombophilia can be observed: antithrombin (0.5 to 4.9 per cent), protein C (1.4 to 8.6 per cent) and protein S (1.4 to 7.5 per cent) deficiencies or factor V Leiden (20 to 30 per cent). Special attention is mandatory in prescribing biological exploration because of the many physiological or pharmacological interferences which can modify the results. Identification of a genetic defect may induce specific management and individuals should receive counselling regarding the implications of this diagnosis. Further prospective studies should help to determine the thrombotic risk in symptomatic and non-symptomatic patients with inherited thrombophilia and the risk/benefit ratio of laboratory screening for hereditary thrombophilia and therapeutic intervention.

[Should the extended evaluation of bronchial adenocarcinoma be different from that of non-small cell lung carcinoma?]. / Le bilan d'extension des adénocarcinomes bronchiques doit-il différer de celui des autres cancers bronchiques non à petites cellules (CBNPC)?

The records of 132 patients explored for initial evaluation of non-small cell lung cancer (NSCLC) were reviewed to find out whether the evaluation of extrathoracic extension could be influenced by anatomicopathological data. Brain, liver and bone metastases were found to be significantly more frequent in adenocarcinomas than in NSCLCs. This relative frequency was observed at all stages, including stages I and II as defined by computerized tomography of the chest, and in asymptomatic patients. We therefore recommend to evaluate fully the tumoral extension in patients with bronchial adenocarcinoma irrespective of its stage, and to do so even in the absence of clinical symptoms.

[Anesthetic management of severe or worsening postpartum hemorrhage]. / Prise en charge anesthésique d'une hémorragie du post-partum sévère ou résistant au traitement médical.

INTRODUCTION: Risk factors of maternal morbidity and mortality during postpartum hemorrhage (PPH) include non-optimal anesthetic management. As the anesthetic management of the initial phase is addressed elsewhere, the current chapter is dedicated to the management of severe PPH. METHODS: A literature search was performed using PubMed and Medline databases, and the Cochrane Library, for articles published from 2003 up to and including 2013. Several keywords related to anesthetic and critical care practice, and obstetrical management were used, in various combinations. Guidelines from several societies and organisations were also read. RESULTS: When PPH worsens, one should ask for additional team personnel (professional consensus). Patients should be monitored for heart rate, blood pressure, skin and mucosal pallor, bleeding at skin puncture sites, diuresis and the volume of genital bleeding (grade B). Because of the possible rapid worsening of coagulapathy, patients should undergo regular evaluation of coagulation status (professional consensus). Prevention and management of hypothermia should be considered (professional consensus), by warming intravenous fluids and blood products, and by active body warming (grade C). Antibiotics should be given, if not already administered at the initial phase (professional consensus). Vascular fluids must be given (grade B), the choice being left at the physician discretion. Blood products transfusion should be decided based on the clinical severity of PPH (professional consensus). Priority is given to red blood cells (RBC) transfusion, with the aim to maintain Hb concentration>8g/dL. The first round of products could include 3 units of RBC (professional consensus), and the following round 3 units of RBC, and 3 units of fresh frozen plasma (FFP). The FFP:RBC ratio should be kept between 1:2 and 1:1 (professional consensus). Depending on the etiology of PPH, the early administration of FFP is left at the discretion of the physician (professional consensus). Platelet count should be maintained at>50 G/L (professional consensus). During massive PPH, fibrinogen concentration should be maintained at>2g/L (professional consensus). Fibrinogen can be given without prior fibrinogen measurement in case of massive bleeding (professional consensus). General anesthesia should be considered in case of hemodynamic instability, even when an epidural catheter is in place (professional consensus). CONCLUSION: The anesthetic management aims to restore and maintain optimal respiratory state and circulation, to treat coagulation disorders, and to allow invasive obstetrical and radiologic procedures. Clinical and instrumental monitoring are needed to evaluate the severity of PPH, to guide the choice of therapeutic options, and to assess treatments efficacy.