Pancytopenia related to acquired sea-blue histiocytosis during chronic parenteral nutrition.

Bone marrow smear showing histiocytes (black arrow) containing sea blue granules stained with May-Grünwald Giemsa.

A focus on dominant negative variants in a series of 170 heterozygous FXI-deficient patients.

INTRODUCTION: Dominant-negative effects have been described for 10 F11 variants in the literature. AIM: The current study aimed at identifying putative dominant-negative F11 variants. MATERIAL AND METHODS: This research consisted in a retrospective analysis of routine laboratory data. RESULTS: In a series of 170 patients with moderate/mild factor XI (FXI) deficiencies, we identified heterozygous carriers of previously reported dominant-negative variants (p.Ser243Phe, p.Cys416Tyr, and p.Gly418Val) with FXI activities inconsistent with a dominant-negative effect. Our findings also do not support a dominant-negative effect of p.Gly418Ala. We also identified a set of patients carrying heterozygous variants, among which five out of 11 are novel, with FXI activities suggesting a dominant-negative effect (p.His53Tyr, p.Cys110Gly, p.Cys140Tyr, p.Glu245Lys, p.Trp246Cys, p.Glu315Lys, p.Ile421Thr, p.Trp425Cys, p.Glu565Lys, p.Thr593Met, and p.Trp617Ter). However, for all but two of these variants, individuals with close to half normal FXI coagulant activity (FXI:C) were identified, indicating an inconstant dominant effect. CONCLUSION: Our data show that for some F11 variants recognized has having dominant-negative effects, such effects actually do not occur in many individuals. The present data suggest that for these patients, the intracellular quality control mechanisms eliminate the variant monomeric polypeptide before homodimer assembly, thereby allowing only the wild-type homodimer to assemble and resulting in half normal activities. In contrast, in patients with markedly decreased activities, some mutant polypeptides might escape this first quality control. In turn, assembly of heterodimeric molecules as well as mutant homodimers would result in activities closer to 1:4 of FXI:C normal range.

Management of rare inherited bleeding disorders: Proposals of the French Reference Centre on Haemophilia and Rare Coagulation Disorders.

INTRODUCTION: The rare coagulation disorders may present significant difficulties in diagnosis and management. In addition, considerable inter-individual variation in bleeding phenotype is observed amongst affected individuals, making the bleeding risk difficult to assess in affected individuals. The last international recommendations on rare inherited bleeding disorders (RIBDs) were published by the United Kingdom Haemophilia Centre Doctors' Organisation in 2014. Since then, new drugs have been marketed, news studies on surgery management in patients with RIBD have been published, and new orphan diseases have been described. AIM: Therefore, the two main objectives of this review, based on the recent recommendations published by the French Reference Centre on Haemophilia and Rare Bleeding Disorders, are: (i) to briefly describe RIBD (clinical presentation and diagnostic work-up) to help physicians in patient screening for the early detection of such disorders; and (ii) to focus on the current management of acute haemorrhages and long term prophylaxis, surgical interventions, and pregnancy/delivery in patients with RIBD.

Multicenter study on recent portal venous system thrombosis associated with cytomegalovirus disease.

BACKGROUND & AIMS: Recent non-malignant non-cirrhotic portal venous system thrombosis (PVT) is a rare condition. Among risk factors for PVT, cytomegalovirus (CMV) disease is usually listed based on a small number of reported cases. The aim of this study was to determine the characteristics and outcomes of PVT associated with CMV disease. METHODS: We conducted a French multicenter retrospective study comparing patients with recent PVT and CMV disease ("CMV positive"; n = 23) to patients with recent PVT for whom CMV testing was negative ("CMV negative"; n = 53) or unavailable ("CMV unknown"; n = 297). RESULTS: Compared to patients from the "CMV negative" and "CMV unknown" groups, patients from the "CMV positive" group were younger, more frequently had fever, and had higher heart rate, lymphocyte count and serum ALT levels (p ≤0.01 for all). The prevalence of immunosuppression did not differ between the 3 groups (4%, 4% and 6%, respectively). Extension of PVT was similar between the 3 groups. Thirteen out of 23 "CMV positive" patients had another risk factor for thrombosis. Besides CMV disease, the number of risk factors for thrombosis was similar between the 3 groups. Heterozygosity for the prothrombin G20210A gene variant was more frequent in "CMV positive" patients (22%) than in the "CMV negative" (4%, p = 0.01) and "CMV unknown" (8%, p = 0.03) groups. Recanalization rate was not influenced by CMV status. CONCLUSIONS: In patients with recent PVT, features of mononucleosis syndrome should raise suspicion of CMV disease. CMV disease does not influence thrombosis extension nor recanalization. More than half of "CMV positive" patients have another risk factor for thrombosis, with a particular link to the prothrombin G20210A gene variant. LAY SUMMARY: Patients with cytomegalovirus (CMV)-associated portal venous system thrombosis have similar thrombosis extension and evolution as patients without CMV disease. However, patients with CMV-associated portal venous system thrombosis more frequently have the prothrombin G20210A gene variant, suggesting that these entities act synergistically to promote thrombosis.

Paroxysmal nocturnal hemoglobinuria and vascular liver disease: Eculizumab therapy decreases mortality and thrombotic complications.

A total of 2%-10% of patients with vascular liver disease (VLD) have paroxysmal nocturnal hemoglobinuria (PNH). Eculizumab reduces complement-mediated haemolytic activity in PNH. This study was aimed at assessing the impact of eculizumab on VLD outcome. Retrospective cohort of PNH patients, in Valdig registry, who had VLD diagnosed between 1997 and 2019 is considered. Eculizumab was the exposure of interest. Studied outcomes were death, venous thrombosis, bleeding, arterial ischemic event, infection, and liver-related complications. We compared survival and new thrombotic events from PNH/VLD cohort to Envie2 non-PNH cohort. Sixty-two patients (33 women), median age 35 years (28-48) and median follow-up VLD diagnosis 4.7 years (1.2-9.5), were included. Clone size was 80% (70-90), median hemoglobin concentration was 10.0 g/dl (8-11), and lactate dehydrogenase (LDH) was 736 IU (482-1744). Forty-two patients (68%) had eculizumab; median exposure time was 40.1 [9.3-72.6] months. Mortality was significantly lower in exposed versus nonexposed period: 2.6 versus 8.7 per 100 (PY), incidence rate ratio (IRR) was 0.29, 95% CI (0.1-0.9), p = .035. Thrombosis recurrence occurred less frequently during the exposure to eculizumab: 0.5 versus 2.8 per 100 PY, IRR 0.22 (0.07-0.64). Other secondary end points (i.e., bleeding, arterial ischemic lesions, infection, and liver complications) were less common during the exposure to eculizumab, although not reaching statistical significance. Six-year thrombosis-free survival was 70%, 95% CI [0.60-0.83] for PNH cohort and 83%, 95% CI [0.70-1.00] for non-PNH Envie 2 patients, (p < .001). In conclusion, patients with PNH and VLD are at higher risk of recurrent thrombosis than non-PNH patients. Eculizumab is significantly associated with a lower mortality and less thrombotic recurrence in patients with PNH and VLD.

Acquired factor V inhibitor: a nation-wide study of 38 patients.

Acquired factor V inhibitor (AFVI) is an extremely rare disorder that may cause severe bleeding. To identify factors associated with bleeding risk in AFVI patients, a national, multicentre, retrospective study was made including all AFVI patients followed in 21 centres in France between 1988 and 2015. All patients had an isolated factor V (FV) deficiency <50% associated with inhibitor activity. Patients with constitutional FV deficiency and other causes of acquired coagulation FV deficiencies were excluded. The primary outcome was incident bleeding and factors associated with the primary outcome were identified. Thirty-eight (74 [36-100] years, 42·1% females) patients with AFVI were analysed. Bleeding was reported in 18 (47·4%) patients at diagnosis and in three (7·9%) during follow-up (7 [0·2-48.7] months). At diagnosis, FV was <10% in 31 (81·6%) patients. Bleeding at diagnosis was associated with a prolonged prothrombin time that strongly correlated with the AFVI level measured in plasma {r = 0·63, 95% confidence interval (CI) [0·36-0·80], P < 0·05}. Bleeding onset during follow-up was associated with a slow AFVI clearance (P < 0·001). The corresponding receiver operating characteristics curve showed that AFVI clearance was predictive of bleeding onset with an AFVI clearance of seven months with a sensitivity of 100% (95% CI: 29-100) and a specificity of 86% (95% CI: 57-98, P = 0·02). Kaplan-Meier analysis showed that AFVI clearance >7 months increased the risk of bleeding by 8 (95% CI: [0·67-97], P = 0·075). Prothrombin time at diagnosis and time for clearance of FV inhibitor during follow-up are both associated with bleeding in patients with AFVI.

Targeting protease nexin-1, a natural anticoagulant serpin, to control bleeding and improve hemostasis in hemophilia.

Hemophilia A and B, diseases caused by the lack of factor VIII (FVIII) and factor IX (FIX) respectively, lead to insufficient thrombin production, and therefore to bleeding. New therapeutic strategies for hemophilia treatment that do not rely on clotting factor replacement, but imply the neutralization of natural anticoagulant proteins, have recently emerged. We propose an innovative approach consisting of targeting a natural and potent thrombin inhibitor, expressed by platelets, called protease nexin-1 (PN-1). By using the calibrated automated thrombin generation assay, we showed that a PN-1-neutralizing antibody could significantly shorten the thrombin burst in response to tissue factor in platelet-rich plasma (PRP) from patients with mild or moderate hemophilia. In contrast, in PRP from patients with severe hemophilia, PN-1 neutralization did not improve thrombin generation. However, after collagen-induced platelet activation, PN-1 deficiency in F8-/-mice or PN-1 blocking in patients with severe disease led to a significantly improved thrombin production in PRP, underlining the regulatory role of PN-1 released from platelet granules. In various bleeding models, F8-/-/PN-1-/- mice displayed significantly reduced blood loss and bleeding time compared with F8-/-mice. Moreover, platelet recruitment and fibrin(ogen) accumulation were significantly higher in F8-/-/PN-1-/- mice than in F8-/-mice in the ferric chloride-induced mesenteric vessel injury model. Thromboelastometry studies showed enhanced clot stability and lengthened clot lysis time in blood from F8-/-/PN-1-/- and from patients with hemophilia A incubated with a PN-1-neutralizing antibody compared with their respective controls. Our study thus provides proof of concept that PN-1 neutralization can be a novel approach for future clinical care in hemophilia.

Efficacy and safety of a recombinant Von Willebrand Factor treatment in patients with inherited Von Willebrand Disease requiring surgical procedures.

INTRODUCTION: Von Willebrand Disease is a common inherited haemorrhagic disorder due to a deficiency of Von Willebrand Factor (VWF). In case of surgical procedures in patients who are not responsive or have contraindications to desmopressin, replacement therapy with VWF concentrates is indicated. Until recently, only plasma-derived VWF concentrates were available. A new recombinant VWF (rVWF) concentrate that contains no Factor VIII (FVIII) but a high amount of high molecular weight VWF multimers has been available in France since 2018. AIM: Describe real-world experience of using rVWF in surgical procedures. METHODS: Sixty-three surgeries for 55 patients were retrospectively analysed in 7 French haemostasis centres. RESULTS: During minor surgeries, the median (range) number of infusions was 1 (1-8) with a preoperative loading dose of 35 (19-56) rVWF IU/kg and a total median dose of 37.5 IU (12-288). During major surgeries, the median (range) number of infusions was only 3 (1-14) with a median preoperative loading dose of 36 IU (12-51) rVWF IU/kg, and a total median dose of 108 IU (22-340) rVWF IU/kg. The overall clinical efficacy was qualified as excellent/good in 61 of the procedures (97%), moderate in 1 (1.5%) and poor in 1 (1.5%). There was no accumulation of VWF or FVIII during postoperative monitoring. No thromboembolic events, anti-VWF antibodies or adverse events were reported. CONCLUSION: This French 'real-world' experience shows that a few infusions and low doses of rVWF provided effective prevention of bleeding in major and minor surgeries in inherited VWD, with no clinically significant safety concerns.

Pregnancy in idiopathic non-cirrhotic portal hypertension: A multicentric study on maternal and fetal management and outcome.

BACKGROUND & AIMS: A total of 15% of patients with idiopathic non-cirrhotic portal hypertension (INCPH) are women of childbearing age. We aimed to determine maternal and fetal outcome of pregnancies occurring in women with INCPH. METHODS: We retrospectively analyzed the charts of women with INCPH followed in the centers of the VALDIG network, having had ≥1 pregnancy during the follow-up of their liver disease. Data are represented as median (interquartile range). RESULTS: A total of 24 pregnancies occurred in 16 women within 24 (5-66) months after INCPH diagnosis. Four women had associated partial portal vein thrombosis before pregnancy. At conception, 2 out of the 16 women had detectable ascites and others were asymptomatic. Out of these 24 pregnancies, there were four miscarriages, one ectopic pregnancy, and one medical termination of pregnancy at 20 weeks of gestation. Out of the 18 other pregnancies reaching 20 weeks of gestation (in 14 patients), there were nine preterm and nine term deliveries. All infants were healthy at delivery, but one died at day 1 of unknown cause and one at day 22 of infectious meningitis; both were preterm. Concerning mothers, two had worsening of ascites, two had variceal bleeding despite non-selective betablockers during pregnancy and one developed a main portal vein thrombosis in early postpartum. Genital bleeding occurred in three patients, including two receiving anticoagulation. All 16 women were alive and asymptomatic after a median follow-up of 27 (9-93) months after last delivery. CONCLUSION: The overall outcome of women with INCPH who become pregnant is favorable despite a significant incidence of complications related to portal hypertension. Fetal outcome is favorable in most pregnancies reaching 20 weeks of gestation. LAY SUMMARY: About 15% of patients with idiopathic non-cirrhotic portal hypertension are women of childbearing age, who can become pregnant. As available reports on pregnancy in these women are scarce and heterogeneous, it is unclear whether or not pregnancy should be contraindicated in this setting. We provide detailed data showing that, regardless of the associated conditions, the overall outcome of women with idiopathic non-cirrhotic portal hypertension becoming pregnant is good despite a significant incidence of complications related to portal hypertension, and that fetal outcome is favorable in most pregnancies reaching 20 weeks of gestation.

Selective testing for calreticulin gene mutations in patients with splanchnic vein thrombosis: A prospective cohort study.

BACKGROUND AND AIMS: Myeloproliferative neoplasms (MPN) are the leading cause of splanchnic vein thrombosis (SVT). Janus kinase 2 gene (JAK2)V617F mutations are found in 80 to 90% of patients with SVT and MPN. Mutations of the calreticulin (CALR) gene have also been reported. However, as their prevalence ranges from 0 to 2%, the utility of routine testing is questionable. This study aimed to identify a group of patients with SVT at high risk of harboring CALR mutations and thus requiring this genetic testing. METHODS: CALR, JAK2V617F and thrombopoietin receptor gene (MPL) mutations were analysed in a test cohort that included 312 patients with SVT. Criteria to identify patients at high risk of CALR mutations in this test cohort was used and evaluated in a validation cohort that included 209 patients with SVT. RESULTS: In the test cohort, 59 patients had JAK2V617F, five had CALR and none had MPL mutations. Patients with CALR mutations had higher spleen height and platelet count than patients without these mutations. All patients with CALR mutations had a spleen height ⩾16cm and platelet count >200×109/L. These criteria had a positive predictive value of 56% (5/9) and a negative predictive value of 100% (0/233) for the identification of CALR mutations. In the validation cohort, these criteria had a positive predictive value of 33% (2/6) and a negative predictive value of 99% (1/96). CONCLUSION: CALR mutations should be tested in patients with SVT, a spleen height ⩾16cm, platelet count >200×109/L, and no JAK2V617F. This strategy avoids 96% of unnecessary CALR mutations testing. Lay summary: Mutations of the CALR gene are detected in 0 to 2% of patients with SVT, thus the utility of systematic CALR mutation testing to diagnose MPN is questionable. This study demonstrates that CALR mutations testing can be restricted to patients with SVT, a spleen height ⩾16cm, a platelet count >200×109/L, and no JAK2V617F. This strategy avoids 96% of unnecessary CALR mutations testing.

Causes and consequences of portal vein thrombosis in 1,243 patients with cirrhosis: results of a longitudinal study.

UNLABELLED: In cirrhosis, portal vein thrombosis (PVT) could be a cause or a consequence of the progression of liver disease. We analyzed data from a prospective trial of ultrasound screening for hepatocellular carcinoma in order to identify risk factors for and the impact of PVT in patients with cirrhosis. In all, 1,243 adults with cirrhosis without PVT were enrolled from 43 liver units in France and Belgium between June 2000 and March 2006. The mean follow-up was 47 months. Doppler ultrasonography was used to check the portal vein. Progression of liver disease was defined by the development of: ascites, hepatic encephalopathy, variceal bleeding, prothrombin <45%, serum bilirubin >45 µmol/L, albumin <28 g/L, and/or creatinine >115 µmol/L. G20210A prothrombin and factor V gene mutations were assessed in sera stored at three large centers. The 5-year cumulative incidence of PVT was 10.7%. PVT was mostly partial and varied over time. The development of PVT was independently associated with baseline esophageal varices (P = 0.01) and prothrombin time (P = 0.002), but not with disease progression before PVT, or prothrombotic mutations. Disease progression was independently associated with baseline age (hazard ratio [HR] 1.55; 95% confidence interval [CI]: 1.11-2.17), body mass index (HR 1.40; 95% CI: 1.01-1.95), prothrombin time (HR 0.79; 95% CI: 0.70-0.90), serum albumin (HR 0.97; 95% CI: 0.94-0.99), and esophageal varices (HR 1.70; 95% CI: 1.21-2.38) but not with the prior development of PVT (HR 1.32; 95% CI: 0.68-2.65). CONCLUSION: In patients with cirrhosis, the development of PVT is associated with the severity of liver disease at baseline, but does not follow a recent progression of liver disease. There is no evidence that the development of PVT is responsible for further progression of liver disease.

Prevention and treatment of atherosclerosis in haemophilia - how to balance risk of bleeding with risk of ischaemic events.

Life expectancy for patients with haemophilia (PWH) has significantly increased in the last decades, due to improvement of clotting factor replacement therapy. However, despite a lower cardiovascular mortality rate and contrasting prevalence for non-fatal ischaemic heart disease (IHD), cardiovascular diseases are increasing in PWH. The prevalence of cardiovascular risk factors in PWH is as prevalent as in the general population, whereas an increased risk of hypertension has been observed in some studies. Furthermore, PWH are not protected against atherosclerosis. Coronary artery disease treatment is extremely challenging in PWH. Two 'institutional' guidelines for the management of IHD in PWH have been published. Since these recommendations, the use of new drugs such as prasugrel, ticagrelor, bivalirudin, new oral anticoagulants and new drug-eluting stents have been recommended in the general population but should be evaluated in PWH. Some questions arise: which trough level during long-term single or dual antiplatelet treatment (DAT) is really needed? The clinical role of platelet testing remains ill defined but may be considered in selected patients. A multidisciplinary approach is necessary for the management of IHD in PWH in order to treat the patient as any patient according to the cardiological guidelines during the acute phase, and long-term management should be discussed.

Type 2 diabetes mellitus as a risk factor for intestinal resection in patients with superior mesenteric vein thrombosis.

BACKGROUND & AIMS: The most serious complication of acute mesenteric vein thrombosis (MVT) is acute intestinal ischaemia requiring intestinal resection or causing death. Risk factors for this complication are unknown. To identify risk factors for severe intestinal ischaemia leading to intestinal resection in patients with acute MVT. METHODS: We retrospectively analysed consecutive patients seen between 2002 and 2012 with acute MVT in 2 specialized units. Patients with cirrhosis were excluded. We compared patients who required intestinal resection to patients who did not. RESULTS: Among 57 patients, a local risk factor was identified in 14 (24%) patients, oral contraceptive use in 16 (29%), and at least one or more other systemic prothrombotic condition in 25 (44%). Five (9%) patients had diabetes mellitus (DM), 33 (58%) had overweight or obesity, 9 (18%) had hypertriglyceridemia and 10 (19%) had arterial hypertension. Eleven patients (19%) underwent intestinal resection. DM was significantly associated with intestinal resection (P = 0.02) while local factors or prothrombotic conditions were not. Computed tomography (CT) scans performed at diagnosis found that occlusion of second order radicles of the superior mesenteric vein was more frequently observed in patients who underwent intestinal resection (P = 0.009). CONCLUSIONS: In acute MVT, patients with underlying DM have an increased risk of requiring intestinal resection. Neither local factors nor systemic prothrombotic conditions are associated with intestinal resection. When CT scan shows the preservation of second order radicles of the superior mesenteric vein, the risk of severe resection is low.

Absorption and efficacy of acetylsalicylic acid in patients with short bowel syndrome.

BACKGROUND: The patients with a short bowel (SB) frequently require antiplatelet therapy. Resection of the bowel is likely to modify the absorption and first-pass effect of drugs. No data on the absorption and efficacy of the cardiovascular dose of aspirin (75-160 mg) in these patients have been published. OBJECTIVE: To evaluate the efficacy of a low dose of aspirin in patients with SB caused by mesenteric ischemia. METHODS: The efficacy of a low dose of aspirin was assessed in 10 consecutive SB patients, both 1 hour and 24 hours after administration (peak and trough value, respectively). The primary criterion was the inhibition of platelet aggregation, as assessed by light transmission aggregometry, triggered with 0.5 mg/mL arachidonic acid. Biological efficacy of aspirin was also evaluated by serum thromboxane B2 value and by platelet function analyzer-100. RESULTS: At its peak value, aspirin had the expected efficacy, as demonstrated both by light transmission aggregometry and the other methods. However, 24 hours after administration, as many as 30% of patients had lost the pharmacological efficacy of their aspirin. CONCLUSION: We show for the first time that with at least 30 cm of small intestine, all patients with SB absorb sufficient oral aspirin in a cardiovascular dose to rapidly exert the expected level of antiplatelet activity. But given only once daily, aspirin does not provide stable 24-hour antiplatelet protection in 30% of patients, because of increased platelet turnover, as usually observed in patients with extensive vascular pathology, diabetes, or inflammation.

The qLabs® FIB system, a novel point-of-care technology for a rapid and accurate quantification of functional fibrinogen concentration from a single drop of citrated whole blood.

Hypofibrinogenemia is often associated with excessive bleeding and requires immediate treatment. The qLabs FIB® is a handheld and easy-to-use point-of-care (POC) device designed for the rapid measurement of functional fibrinogen concentration from a single drop of citrated whole blood. The aim of this study was to evaluate the analytical performances of the qLabs FIB system. Fibrinogen concentrations from 110 citrated whole blood specimen were measured by both the qLabs FIB and the Clauss laboratory reference methods (STA®-Liquid Fib assay on STA-R® Max from Stago). A three-laboratories comparison study was conducted to assess reproducibility and repeatability of the qLabs FIB using plasma quality control material. In addition, single-site assays were conducted to assess the repeatability from citrated whole blood specimen covering the qLabs FIB reportable range. A very strong correlation between the qLabs FIB and the Clauss laboratory reference method was observed (r = 0.95). Using a clinical cut-off value of 2.0 g/L, the area under the receiver operating characteristic curve (ROC) of citrated whole blood was 0.99 and sensibility and specificity were 100 % and 93.5 %, respectively. Percent CVs for reproducibility and repeatability assessed from quality control material, were both <5 %. Repeatability assessed from citrated whole blood specimen showed a CV of 2.6 to 6.5 %. In conclusion, the qLabs FIB system enables a rapid and reliable measurement of functional fibrinogen levels from citrated whole blood and exhibits a strong prediction power at the 2 g/L clinical cut-off when compared to the Clauss laboratory reference. Further clinical studies should demonstrate its ability to quickly confirm the diagnosis of acquired hypofibrinogenemia and help identify patients who may benefit from targeted hemostatic treatment.

Surgery in rare bleeding disorders: the prospective MARACHI study.

Background: Despite the wide use of bleeding scores and the reliability of clotting factor level measurement, bleeding risk stratification before surgery remains challenging in patients with rare inherited bleeding disorders. Objectives: This multicenter observational prospective study assessed in patients with rare coagulation factor deficiency, the perioperative hemostatic management choices by hemostasis experts and the bleeding outcomes after surgery. Methods: One hundred seventy-eight patients with low coagulation activity level (factor [F] II, FV, combined FV-FVIII, FVII, FX, or FXI <50%) underwent 207 surgical procedures. The bleeding outcome, Tosetto's bleeding score, and perioperative hemostatic protocols were collected. Results: Among the 81 procedures performed in patients with severe factor deficiency (level ≤10%), 27 were done without factor replacement (including 6 in patients at high bleeding risk), without any bleeding event. Factor replacement therapy was used mainly for orthopedic procedures. In patients with mild deficiency, 100/126 surgical procedures were carried out without perioperative hemostatic treatment. In patients with FVII or FXI deficiency, factor replacement therapy was in function of the procedure, bleeding risk, and to a lesser extent previous bleeding history. Tranexamic acid was used in almost half of the procedures, particularly in case of surgery in tissues with high fibrinolytic activity (76.8%). Conclusions: The current perioperative hemostatic management of patients with rare bleeding disorders appears to be adapted. Among the 207 procedures, only 6 were associated with excessive bleeding. Our findings suggest that rather than the bleeding score, factor level and surgery type are the most relevant criteria for perioperative factor replacement therapy.