Congenital fibrinogen disorders.

Congenital fibrinogen disorders are rare pathologies of the haemostasis, comprising afibrinogenaemia, hypofibrinogenaemia, dysfibrinogenaemia and hypodysfibrinogenaemia. Phenotypic manifestations are variable, patients may be asymptomatic or suffer from bleeding or thrombosis. Most of congenital fibrinogen disorders are coincidentally discovered. Fibrinogen concentrate is used to treat bleeding, whereas low-molecular weight heparin is most often administered for the treatment of thrombotic complications. The aim of this review is to provide an update of the knowledge of congenital fibrinogen disorders for Danish physicians.

Management of pregnancy and delivery in congenital fibrinogen disorders: communication from the ISTH SSC Subcommittee on Factor XIII and Fibrinogen.

Congenital fibrinogen disorders (CFDs) are a heterogeneous group of rare congenital quantitative and/or qualitative fibrinogen deficiencies. The spectrum of molecular anomalies is broad, leading to several subtypes of fibrinogen disorders (ie, afibrinogenemia, hypofibrinogenemia, dysfibrinogenemia, and hypodysfibrinogenemia). Pregnancy in women with CFDs is a high-risk clinical situation, with an increased tendency for miscarriages, bleeding, and thrombosis. Even though it is well established that management of such pregnancies requires a multidisciplinary approach involving specialists (hematologists and maternal/fetal medicine experts with expertise in the management of inherited bleeding disorders), specific guidelines are lacking. In this International Society on Thrombosis and Haemostasis (ISTH) Scientific and Standardization Committee communication, we aim to propose an expert consensus opinion with literature evidence where available on the strategy for management of pregnancy, delivery, and puerperium in CFDs.

[Placenta percreta management in a patient with a severe congenital hypofibrinogenemia]. / Gestion d'un placenta percreta chez une patiente atteinte d'une hypofibrinogénémie congénitale sévère.

The obstetrical follow-up of patients with a severe hypofibrinogenemia requires a multidisciplinary collaboration because of potential maternal-fetal complications (recurrent miscarriages, intrauterine fetal demise, post-partum hemorrhage, thrombosis). We report the obstetrical management of a multiparous patient with a severe congenital hypofibrinogenemia associated with a platelet disorder (abnormal phospholipid externalization). A therapeutic strategy based on a biweekly administration of fibrinogen concentrates associated with enoxaparin and aspirin allowed the maintenance of pregnancy. But this last one got complicated by a placenta percreta requiring a salvage hysterectomy with an appropriate hemorrhage prophylaxis.

Hypofibrinogenemic Massive Transfusion Trauma Patients Experience Worse Outcomes.

INTRODUCTION: Uncontrolled hemorrhage accounts for up to 40% of trauma-related mortality. Previous reports demonstrate that decreased fibrinogen levels during traumatic hemorrhage are associated with worse outcomes. Cryoprecipitate is used to replace fibrinogen for patients in hemorrhagic shock undergoing massive transfusion (MT), though the optimal ratio of cryoprecipitate to fresh frozen plasma (FFP), packed red blood cells (PRBCs), and platelets remains undefined. The purpose of this study is to investigate the effect of admission fibrinogen level and the use of cryoprecipitate on outcomes in trauma patients undergoing MT. METHODS: A prospective practice management guideline was established to obtain fibrinogen levels on adult trauma patients undergoing MT at a level I trauma center from December 2019 to December 2021. Ten units of cryoprecipitate were administered every other round of MT. Thromboelastography (TEG) was also obtained at the initiation and completion of MT. Patient demographic, injury, transfusion, and outcome data were collected. Hypofibrinogenemic (<200 mg/dL) patients at initiation of MT were compared to patients with a level of 200 mg/dL or greater. RESULTS: A total of 96 out of 130 patients met criteria and underwent MT with a median admission fibrinogen of 170.5 mg/dL. Hypofibrinogenemia was associated with elevated INR (1.26 vs 1.13, P < .001) and abnormal TEG including decreased alpha angle (68.1 vs 73.3, P < .001), increased K time (1.7 vs 1.1, P < .001), and decreased max amplitude (58 vs 66, P < .001). Patients with hypofibrinogenemia received more PRBC (10 vs 7 U, P = .002), FFP (9 vs 6 U, P = .003), and platelets (2 vs 1 U, P = .004) during MT. Hypofibrinogenemic patients demonstrated greater mortality than patients with normal levels (50% vs 23.5%, P = .021). Older age, decreased GCS, and elevated injury severity score (ISS) were risk factors for mortality. Increased fibrinogen was associated with lower odds of mortality (P = .001). Age, ISS, and fibrinogen level remained significantly associated with mortality in a multivariable analysis. Overall, fibrinogen in post-MT survivors showed an increase in median level compared to admission (231 vs 177.5 mg/dL, P < .001). CONCLUSION: Trauma patients undergoing MT with decreased admission fibrinogen demonstrate increased mortality. Other mortality risk factors include older age, decreased GCS, and higher ISS. Patients with increased fibrinogen levels had lower odds of mortality in a multivariable model. Post-MT survivors demonstrated significantly higher fibrinogen levels than pre-MT patients. Hypofibrinogenemic patients also had worse TEG parameters and required more PRBCs, FFP, and platelets during MT. Further studies are needed to assess the optimal volume of fibrinogen replacement with cryoprecipitate during MT to improve trauma patient mortality.

Transfusion of fibrinogen concentrate before dental extractions in patients with afibrinogenemia: a narrative review supported by a case report with a proposed treatment protocol.

Afibrinogenemia is a coagulation disorder that occurs with a frequency of 1-2 cases/1,000,000 population and is characterized by a lack of capacity to synthesize fibrinogen. The predominant symptoms related to fibrinogen deficiency are mucocutaneous bleeding, bleeding from the gastrointestinal tract, genital tract or other vascularized tissues as well as excessive bleeding after minor injuries or accidental cuts. Thromboembolic complications and impaired wound healing may also occur. Due to the rarity of the disease, there are no recommendations about fibrinogen substitution before dental procedures (including dental surgery). The purpose of this review is to discuss the indications for the transfusion of a coagulation factor in the preparation of a patient with afibrinogenemia for dental extraction. The article is a narrative review with a proposed management protocol for the dental procedure. The authors have included information from previously published case reports, research studies, and review papers as well as their own case report.

One Hundred Years of Congenital Fibrinogen Disorders.

Congenital fibrinogen disorders encompass a broad range of fibrinogen defects characterized by a wide molecular and clinical spectrum. From the first clinical description of afibrinogenemia in 1920, many major achievements have contributed to a better understanding of these complex disorders. The finding of causative mutations in all three fibrinogen genes has contributed to reveal the molecular mechanisms involved in biosynthesis of the fibrinogen molecule and to clarify the basic processes of fibrin polymerization and fibrinolysis. The compilation of abundant cases with detailed genetic, biological, and clinical features has enabled the classification of congenital fibrinogen disorders into several types and subtypes. Thus, the recent classification of congenital fibrinogen disorder is based not only on the clottable and antigenic fibrinogen levels but also on the patient's clinical phenotype and genotype. Fibrinogen supplementation is the cornerstone of bleeding management in fibrinogen disorders. Since the discovery of blood fractionation, the method of production of fibrinogen concentrate has been progressively modified to significantly improve purity and safety. Nevertheless, the availability of such products is still limited to a few countries and the optimal threshold of fibrinogen to target is still not established. In this review, we describe the major advances that have characterized 100 years of congenital fibrinogen disorders, focusing on afibrinogenemia and dysfibrinogenemia.

Overt Disseminated Intravascular Coagulation with Severe Hypofibrinogenemia During Veno-Venous Extracorporeal Membrane Oxygenation.

Disseminated intravascular coagulation (DIC) is a life-threatening hematologic derangement characterized by dysregulated thrombin generation and excessive fibrinolysis. However, DIC is poorly characterized in the extracorporeal membrane oxygenation (ECMO) population, and the underlying mechanisms are not well understood. Several mechanisms contribute to DIC in ECMO, including consumption of coagulation factors, acquired von Willebrand's syndrome leading to thrombocytopenia, and hyperfibrinolysis. There are few case reports of DIC in adult ECMO patients. Most are in the context of venoarterial ECMO, which is typically used in the setting of cardiogenic shock and cardiac arrest. These disease states themselves are known to be associated with DIC, liver failure, impaired anticoagulant mechanisms, and increased fibrinolysis. We present an unusual case of a 74-year-old man who developed overt DIC during veno-venous (VV) ECMO. DIC resulted in clinical bleeding and severe hypofibrinogenemia requiring massive cryoprecipitate transfusion of 87 pooled units. When the patient was decannulated from ECMO, his platelet count and fibrinogen concentration improved within 24 hours, suggesting that ECMO was a proximate cause of his DIC.

Role of Fibrinogen in Trauma-Induced Coagulopathy.

BACKGROUND: Fibrinogen is the first coagulation factor to decrease after massive hemorrhage. European massive transfusion guidelines recommend early repletion of fibrinogen; however, this practice has not been widely adopted in the US. We hypothesize that hypofibrinogenemia is common at hospital arrival and is an integral component of trauma-induced coagulopathy. STUDY DESIGN: This study entailed review of a prospective observational database of adults meeting the highest-level activation criteria at an urban level 1 trauma center from 2014 through 2020. Resuscitation was initiated with 2:1 red blood cell (RBC) to fresh frozen plasma (FFP) ratios and continued subsequently with goal-directed thrombelastography. Hypofibrinogenemia was defined as fibrinogen below 150 mg/dL. Massive transfusion (MT) was defined as more than 10 units RBC or death after receiving at least 1 unit RBC over the first 6 hours of admission. RESULTS: Of 476 trauma activation patients, 70 (15%) were hypofibrinogenemic on admission, median age was 34 years, 78% were male, median New Injury Severity Score (NISS) was 25, and 72 patients died (15%). Admission fibrinogen level was an independent risk factor for MT (odds ratio [OR] 0.991, 95% CI 0.987-0.996]. After controlling for confounders, NISS (OR 1.034, 95% CI 1.017-1.052), systolic blood pressure (OR 0.991, 95% CI 0.983-0.998), thrombelastography angle (OR 0.925, 95% CI 0.896-0.954), and hyperfibrinolysis (OR 2.530, 95% CI 1.160-5.517) were associated with hypofibrinogenemia. Early cryoprecipitate administration resulted in the fastest correction of hypofibrinogenemia. CONCLUSION: Hypofibrinogenemia is common after severe injury and predicts MT. Cryoprecipitate transfusion results in the most expeditious correction. Earlier administration of cryoprecipitate should be considered in MT protocols.

Hypofibrinogenaemia and hypocalcaemia in adult trauma patients receiving pre-hospital packed red blood cell transfusions: Potential for supplementary pre-hospital therapeutic interventions.

OBJECTIVE: To report the arrival ionised calcium (iCa) and fibrinogen concentrations in trauma patients treated with packed red blood cells by the road-based high-acuity response units of a metropolitan ambulance service. METHODS: A retrospective review of trauma patients treated with packed red blood cells by high-acuity response units between January 2012 and December 2016. Patients were identified from databases at southeast Queensland adult trauma centres, Pathology Queensland Central Transfusion Laboratory, Gold Coast University Hospital blood bank and the Queensland Ambulance Service. Patient characteristics, results of laboratory tests within 30 min of ED arrival were analysed. RESULTS: A total of 164 cases were analysed. The median injury severity score was 33.5 (interquartile range 22-41), with blunt trauma the commonest mechanism of injury (n = 128, 78.0%). Fifty-eight of the 117 patients (24.4%) with fibrinogen measured had a fibrinogen concentration ≤1.5 g/L; 79 of the 123 patients (64.2%) with an international normalised ratio (INR) measurement had an INR >1.2; 97 of 148 patients (63.8%) with an iCa measured, had an iCa below the Pathology Queensland reference range of 1.15-1.32 mmol/L. Arrival fibrinogen concentration ≤1.5 g/L and arrival iCa ≤1.00 were associated with in-hospital mortality with odds ratio 11.90 (95% confidence interval 4.50-31.65) and odds ratio 4.97 (95% confidence interval 1.42-17.47), respectively. CONCLUSIONS: Hypocalcaemia and hypofibrinogenaemia on ED arrival were common in this cohort. Future work should evaluate whether outcomes improve by correction of these deficits during the pre-hospital phase of trauma care.

Congenital Fibrinogen Deficiency in India and Role of Human Fibrinogen Concentrate.

Congenital fibrinogen deficiency is an inherited disorder due to genetic mutations with diverse presentations arising from reduced fibrinogen levels (hypofibrinogenemia), absence of fibrinogen in circulation (afibrinogenemia), abnormal functioning (dysfibrinogenemia) or both reduced levels and abnormal functioning (hypodysfibrinogenemia) of fibrinogen. The decreased fibrinogen concentration in congenital fibrinogen deficiency necessitates fibrinogen replacement therapy with fresh frozen plasma, cryoprecipitate, or human fibrinogen concentrate. However, the use of fresh frozen plasma and cryoprecipitate is limited owing to their longer transfusion time, requirement of high doses, volume overload, risk of viral transmission, and other safety concerns. The availability of human fibrinogen concentrate has made it the preferred replacement alternative due to its reduced risk of viral transmission, smaller infusion volume, and accurate dosing. The hemostatic efficacy and safety of human fibrinogen concentrate in congenital fibrinogen deficiency is well established in the literature. We review the prevalence of congenital fibrinogen deficiency in India and the current role of human fibrinogen concentrate in its management.

Acquired hypofibrinogenemia in a patient with multiple myeloma.

We report a case of acquired hypofibrinogenemia with multiple myeloma presenting λ-type IgG monoclonal protein. The patient had anemia and renal deficiency, and also developed bleeding tendency due to severe coagulopathy. Her fibrinogen level was under the detectable limits in a functional assay. Enzyme-linked immunosorbent assay (ELISA) and immunoblotting analysis results were consistent with functional assay results, and deficiency patterns observed in cross-mixing tests for PT and aPTT confirmed the diagnosis of hypofibrinogenemia. To determine the cause of hypofibrinogenemia, we purified the patient's immunoglobulin via protein A agarose, and confirmed that fibrinogen was included in the bound fraction, strongly indicating paraprotein interference with fibrinogen. As accelerated removal of fibrinogen was indicated, we incubated the patient's plasma up to 48 h, but did not observe significant loss of fibrinogen. In sharp contrast, fibrinogen returned to below the detection level 12 h after infusion of fresh frozen plasma. These findings support leukocyte-mediated fibrinogen removal, rather than paraprotein-triggered fibrinogen instability. Surprisingly, the patient's paraprotein was IgG2, but we speculate the amount of paraprotein (IgG 5346 mg/dL) compensated for lower affinity to Fcγ receptors.

How I treat dysfibrinogenemia.

Congenital dysfibrinogenemia (CD) is caused by structural changes in fibrinogen that modify its function. Diagnosis is based on discrepancy between decreased fibrinogen activity and normal fibrinogen antigen levels and is confirmed by genetic testing. CD is caused by monoallelic mutations in fibrinogen genes that lead to clinically heterogenous disorders. Most patients with CD are asymptomatic at the time of diagnosis, but the clinical course may be complicated by a tendency toward bleeding and/or thrombosis. Patients with a thrombosis-related fibrinogen variant are particularly at risk, and, in such patients, long-term anticoagulation should be considered. Management of surgery and pregnancy raise important and difficult issues. The mainstay of CD treatment remains fibrinogen supplementation. Antifibrinolytic agents are part of the treatment in some specific clinical settings. In this article, we discuss 5 clinical scenarios to highlight common clinical challenges. We detail our approach to establishing a diagnosis of CD and discuss strategies for the management of bleeding, thrombosis, surgery, and pregnancy.

Effect of hypofibrinogenemia on obstetrical disseminated intravascular coagulation in Japan in 2018: a multicenter retrospective cohort study.

Japanese obstetrical hemorrhage recommendations state that not only pregnant women with an obstetrical disseminated intravascular coagulation (DIC) score ≥ 8 points but also those with fibrinogen levels ≤ 1.5 g/L have a high risk of maternal death and warrant blood transfusion. Our aim was to demonstrate the potential of fibrinogen levels ≤ 1.5 g/L as predictors of a Japanese obstetrical DIC score of ≥ 8. We included 595 participants with blood loss ≥ 1000 mL during vaginal delivery or ≥ 2000 mL during cesarean delivery. The frequency and volume of red blood cell (RBC), fresh-frozen plasma, platelet concentrate (PC), and fibrinogen administration in women with a DIC score of ≥ 8 and fibrinogen levels of ≤ 1.5 g/L were significantly higher than controls (P < 0.0001). Multivariate analysis demonstrated that a score of ≥ 3 was associated with RBC or fibrinogen administration and a score of ≥ 5 was associated with PC transfusion. Fibrinogen levels ≤ 1.89 g/L and ≤ 2.44 g/L were associated with PC transfusion and fibrinogen administration, respectively. Fibrinogen levels ≤ 1.5 g/L may have similar potential to a DIC score of ≥ 8 points for detecting obstetrical DIC in Japan.

Transfusion with Cryoprecipitate for Very Low Fibrinogen Levels Does Not Affect Bleeding or Survival in Critically Ill Cirrhosis Patients.

BACKGROUND: Fibrinogen (FIB) levels less than 150 mg/dL have been associated with increased rates of bleeding and lower survival in critically ill cirrhosis patients. OBJECTIVE: We aimed to determine if treatment with cryoprecipitate (CRYO) for low FIB levels is associated with bleeding outcomes or survival. METHODS: A total of 237 cirrhosis patients admitted to an intensive care unit at a tertiary care liver transplant center with initial FIB levels less than 150 mg/dL were retrospectively assessed for CRYO transfusion, bleeding events, and survival outcomes. RESULTS: The mean MELD score was 27.2 (95% confidence interval [CI]: 26.0-28.3) and CLIF-C acute on chronic liver failure score was 53.4 (51.9-54.8). Ninety-nine (41.8%) were admitted for acute bleeding and the remainder were admitted for nonbleeding illnesses. FIB level on admission correlated strongly with disease severity. After adjusting for disease severity, FIB on admission was not an independent predictor of 30-day survival (hazard ratio [HR]: 0.99, 95% CI: 0.99-1.01, p = 0.68). CRYO transfusion increased FIB levels but had no independent effect on mortality or bleeding complications (HR: 1.10, 95% CI: 0.72-1.70, p = 0.65). CONCLUSION: In cirrhosis patients with critical illness, low FIB levels on presentation reflect severity of illness but are not independently associated with 30-day mortality. Treatment of low FIB with CRYO also does not affect survival or bleeding complications, suggesting FIB is an additional marker of severity of illness but is not itself a direct factor in the pathophysiology of bleeding in critically ill cirrhosis patients.

Heterogeneity of congenital afibrinogenemia, from epidemiology to clinical consequences and management.

Fibrinogen is a complex protein playing a major role in coagulation. Congenital afibrinogenemia, characterized by the complete absence of fibrinogen, is associated with major hemostatic defects. Even though the clinical course is unpredictable and can be completely different among patients, severe bleeding is the prominent symptom. Patients are also at increased risk of thrombosis and sometimes suffer from spontaneous spleen rupture, bone cysts and defective wound healing. Due to the relative rarity of afibrinogenemia, there are no evidence-based strategies for helping physicians in care of these patients. Fibrinogen supplementation is the keystone to prevent or treat bleeding events. In addition, fibrinogen, a pleiotropic protein with numerous physiological roles in immunity, angiogenesis and tissue repair, is involved in many diseases. Indeed, depletion of fibrinogen in animal models of infections, tumors and neurological diseases has an effect on the clinical course. The consequences for patients with afibrinogenemia still need to be investigated.

Severe hypofibrinogenemia in patients bitten by Gloydius tsushimaensis in Tsushima Island, Nagasaki, Japan, and treatment strategy.

Gloydius tsushimaensis is an endemic species inhabiting only Tsushima, a remote Japanese island, and is a distinct species from Gloydius blomhoffii widely distributed throughout mainland Japan and Gloydius brevicaudus and Gloydius ussuriensis which are geographically distributed in South Korea. This is the first multicenter retrospective study of G. tsushimaensis bites in Japan. A study of seventy-two patients who visited the former Izuhara Hospital, the former Naka Tsushima Hospital, Tsushima Hospital, and Kamitsushima Hospital during the fourteen years from January 1, 2005, to December 31, 2018, revealed the typical clinical characteristics of G. tsushimaensis bites. Five out of seventy-two cases (6.9%) showed severe hypofibrinogenemia, in which fibrinogen levels were below 100 mg/dl, which is an unreported clinical finding for G. blomhoffii bites. Generally, when fibrinogen levels are lower than 100 mg/dl, the bleeding risk increases, and it is perilous. Severe hypofibrinogenemia cases did not improve after G. blomhoffii antivenom administration. Additionally, all five cases had disseminated intravascular coagulation, and there were two cases of acute kidney injury and one death. five cases had a median maximum creatine kinase level of 5171 IU/l (Interquartile range: 4992-41,310). Although the mechanism is not precise, coagulation tests showed that the G. tsushimaensis venom contains a thrombin-like enzyme. Based on this research, we created an algorithm for the treatment of G. tsushimaensis bites and unified the treatment methods used on the island.

Congenital dysfibrinogenaemia presented with preterm premature rupture of the membranes and vaginal bleeding.

A 26-year-old woman was found to have congenital dysfibrinogenaemia after presenting to our hospital with premature rupture of the membranes and vaginal bleeding. Given the absence of clear guidelines for the management of pregnancy complicated by dysfibrinogenaemia, we followed expert consensus that exists among published works, with some modifications. This case was managed by a multidisciplinary team of obstetrics-gynaecology, haematology and paediatric haematology. Here we review how the patient presented, the investigations that led to the diagnosis and the treatment options.

Bleeding characteristics and management of minor surgeries in rare bleeding disorders: report from a Turkish Pediatric Hematology Center.

BACKGROUND AND OBJECTIVES: In this retrospective report the aim was to present the experience about bleeding characteristics and management of minor surgeries in rare bleeding disorders (RBDs). METHODS: Twenty-six patients were included; with Factor (F) V, FV+VIII, VII, FXI deficiency and afibrinogenemia. Six of the patients were asymptomatic. RESULTS: Fifty-three percent of the patients suffered from mucosal bleeding. Life-threatening bleedings were observed only in the patients with afibrinogenemia and good hemostatic control could only be provided with plasma-derived (pd)-fibrinogen concentrate. Twelve of the patients had undergone 17 minor surgeries. In the patients with FVII and FXI deficiencies with plasma F:C activity between 20-47%, there was a history of uneventful tooth extractions, circumcisions and a pilonidal sinus operation performed without any replacement treatment, whereas one patient with plasma F:C activity of FVII 47% had a history of poor hemostatic control during an adeno-tonsillectomy operation. Although some of these patients were asymptomatic to be on the safe side, minor operations were performed with preoperative administration of one dose of (pd)-fibrinogen concentrate to one afibrinogenemia patient, recombinant active FVII (rFVIIa) to 2 FVII deficient patients and fresh frozen plasma (FFP) to 3 FXI deficient and 1 FVII deficient patients plus postoperatively tranexamic acid (TXA) for 5-7 days. Only with one dose of the replacement therapy just before surgeries good hemostatic control was achieved and none of them had bleeding neither during nor after the surgeries. CONCLUSION: We suggest that minor operations must be performed with preoperative replacement therapies plus 5-7 days of antifibrinolytics under close observation of the hematologist and the surgeon.

Women With Congenital Hypofibrinogenemia/Afibrinogenemia: From Birth to Death.

Congenital fibrinogen disorders are a group of most frequent rare coagulation disorder, characterized by deficiency and/or defects in the fibrinogen molecule. Quantitative disorders include hypofibrinogenemia and afibrinogenemia. Due to their specific physiological characteristics, female patients tend to have congenital hypofibrinogenemia/afibrinogenemia, such as spontaneous recurrent abortion, menorrhagia, infertility, antepartum and postpartum hemorrhage, and so on. Current studies of congenital hypofibrinogenemia/afibrinogenemia mainly focus on different types of fibrinogen mutations, etiology/pathogenesis, and some rare case reports of the diseases. So far, there is no study available to systematically review the specific features of female patients with congenital bleeding disorders. This review aims to deal with hematological, gynecologic and obstetric issues, and relevant clinical management of congenital hypofibrinogenemia/afibrinogenemia at different life stages of female patients. We believe this review provides valuable reference for clinicians in the field of hematology, obstetrics, as well as gynecology.

Trials and Tribulations of Viscoelastic-Based Determination of Fibrinogen Concentration.

Acquired fibrinogen deficiency is a major determinant of severe bleeding in different clinical conditions, including cardiac surgery, trauma, postpartum hemorrhage, liver surgery, and transplantation. The existing guidelines recommend to supplement fibrinogen in patients with severe bleeding when the fibrinogen concentration is <1.5 g/L. Viscoelastic tests (VETs) provide a fast determination of the fibrinogen contribution to clot firmness and allow prompt treatment of acquired fibrinogen deficiency. However, different VET devices are presently available on the market, based on different technologies and different activators and platelet inhibitors. The available tests are the functional fibrinogen (FF, thromboelastography), the fibrinogen contribution to clot firmness (fibrinogen determination [FIBTEM], thromboelastometry), and the fibrinogen contribution to clot strength (FCS, sonorheometry). All these tests have a moderate to very good correlation with the Clauss fibrinogen assays; however, when comparing VET-based fibrinogen contribution to clot firmness with Clauss fibrinogen concentration, strong differences occur within the same test under different conditions and between different tests. The most widely studied test is the thromboelastometric FIBTEM; the best predictor of a Clauss fibrinogen <1.5 g/L is placed at a maximum clot firmness around 8 mm of amplitude. Fewer data are available for thromboelastographic FF, but the correspondent value is in the range of 12 mm. Overall, due to an incomplete inhibition of platelet contribution, FF overestimates the fibrinogen contribution with respect to FIBTEM. Data on sonorheometry FCS are limited and conflicting. When addressing the correlation between different tests, it is good in general, but no fixed conversion factors can be proposed, due to a considerable dispersion of the experimental points. In conclusion, VET-based fibrinogen tests are certainly powerful tools that are presently suggested by the existing guidelines; however, when using them for clinical decision-making, users should consider the possible sources of bias, which include the different level of platelet inhibition, the role of platelet count and function, the possible different degrees of blood activation with tissue factor, the important role of factor XIII in stabilizing the fibrin clot, and others.