Introduction
Acquired haemophilia A (AHA) is a rare autoimmune bleeding disorder caused by the presence of autoantibodies against coagulation factor VIII (FVIII). The mortality rate remains high. ...International recommendations define complete remission as undetectable inhibitor (<0.6 Bethesda Units BU) and normal FVIII activity (FVIII:C) that persists after immunosuppressive therapy stopped. For patients achieving remission, the risk of relapse reaches 20%. The risk factors for this relapse are not well known.
Aim
In this study, we examined the accuracy of the FVIII/W ratio (FVIII:C/von Willebrand Factor Antigen (VWF:Ag) ratio) to predict relapse in 64 consecutive patients with AHA.
Results
In this cohort, all patients had a very low FVIII/W ratio at the time of diagnosis, and this value progressively increased in the first weeks of immunosuppressive treatment. In our study, 9/55 (14%) did not achieve complete remission. Twenty‐seven patients were followed long enough (more than a year) to show that in the 22 patients who did not relapse, the FVIII/W ratio remained durably normalized. By contrast, in the five patients who relapsed during follow‐up, we noted either no normalization of the FVIII/W ratio, or a secondary decrease to an abnormal value of <0.7 after initial normalization. In all patients who relapsed, the ratio was the first abnormal biological result to be observed, always preceding changes in the activated partial thromboplastin time (aPTT), FVIII:C and anti‐FVIII reappearance.
Conclusion
These data suggest that the FVIII/W ratio could be considered a sensitive biological marker to predict recovery and/or relapse in AHA.
Summary
This FranceCoag network study assessed 33 patients with congenital factor XIII (FXIII) deficiency presenting FXIII levels <10 iu/dl. Diagnosis was based on abnormal bleeding in 29 patients, a ...positive family history in 2, recurrent miscarriages in 1 and was fortuitous in 1. Eighteen patients (62·1%) presented life‐threatening umbilical or intracranial haemorrhages (ICH). Seven of the 15 patients who experienced ICH were diagnosed but untreated, including 3 with secondary neurological sequelae. All pregnancies without prophylaxis (26/26) led to miscarriages versus 3/16 with prophylaxis. In patients exhibiting FXIII levels <10 iu/dl, prophylaxis could be discussed at diagnosis and at pregnancy. Further controlled prospective studies are needed.
Good syndrome (GS) is a rare condition in which thymoma is associated with hypogammaglobulinemia. It is characterized by increased susceptibility to bacterial, viral, and fungal infections, as well ...as autoimmunity. Most patients have no circulating B cells.
The French DEFicit Immunitaire de l'adulte cohort provides detailed clinical and immunological descriptions of 690 adults with primary hypogammaglobulinemia. Comparisons between patients with GS, those with common variable immunodeficiency (CVID), and those with B(-) CVID (circulating B cells <1%) were performed.
Twenty-one patients had GS and 440 had CVID, including 39 B(-) CVID, with a median age at diagnosis of 60, 35, and 34 years, respectively. Invasive bacterial infections were observed in 90.5% of GS, 54% of CVID, and 72% of B(-) CVID patients. Eight patients with GS had opportunistic infections, despite normal peripheral CD4(+) T-cell numbers. Autoimmune complications were demonstrated in 76% of GS, 29% of CVID, and 26% of B(-) CVID patients. The spectrum of autoimmunity in GS was uncommon, consisting of oral lichen planus, graft-vs-host disease-like colitis, and pure red cell aplasia, different from the pattern observed in CVID patients. GS patients did not display lymphoid hyperplasia nor lymphoma, unlike those with CVID or B(-) CVID.
GS differs notably from CVID and B(-) CVID: very late onset, no familial cases, and absence of lymphoid hyperplasia. The key observation is the very high frequency of invasive bacterial infections in GS, an issue that physicians should be aware of.
Introduction: In the last decades, the life expectancy of patients with hemophilia A (HA), hemophilia B (HB) and von Willebrand disease (VWD) has substantially improved. As a result, these patients ...experience age-related comorbidities, especially ischaemic heart disease. Safety and efficacy of antiplatelet drugs in patients with inherited bleeding disorders remain unclear, while there is no evidence-based guideline for the antithrombotic management in this population. The aims of our study were to describe the management of patients with HA, HB and VWD at the occurrence of ischaemic heart disease in our regional referral center; to compare this management to experts' recommendations; and to evaluate the safety and the efficacy of antiplatelet drugs in this population.
Methods: The source of population was the 2008-2018 cohort of patients with HA (n=565), HB (n=115) and VWD (n=618) followed at Toulouse University hospital (France). Their follow-up is recorded in electronic medical files. We retrospectively identified the patients who experienced an ischaemic heart disease treated by antiplatelet therapy. Ischaemic heart disease included ST- and non-ST-segment elevation acute myocardial infarction, stable and unstable angina, and silent coronary artery disease. We described the reperfusion therapy, the use of antiplatelet drugs and replacement factors, and the occurrence of bleeding or thrombotic complications during the follow-up.
Results: Eight patients had an ischaemic heart disease: 5 HA, 1 HB and 2 VWD patients. Four of the haemophilic patients had minor hemophilia; the two others had moderate hemophilia. VWD patients were one type 1 (FVIII 26%, VWF:Ag 13%) and one type 2B (FVIII 29%, VWF:Ag 75%, VWF :Act 24%, low platelet count). Age at the time of the cardiac event ranged from 49 to 80 years. All patients were men except the patient with type 2B VWD. Cardiovascular risk factors were frequent (overweight, n=5; hypercholesterolemia, n=4; smoking, n=4). Four patients were investigated because of cardiac symptoms (unstable angina, angina, dyspnea, palpitations, n=1 each), and one patient because of family history. The last 3 patients were investigated as part of a screening program including patients with a high cardiovascular risk estimation.
The initial management was as follows: 4 patients underwent a percutaneous coronary intervention (PCI) and 4 had a triple coronary artery bypass grafting (CABG). All patients treated with PCI had dual antiplatelet therapy for one month, then low-dose aspirin. CABG patients were initiated with low-dose aspirin. FVIII exposure was lower in PCI patients than in CABG patients (13 ± 10.42 versus 19 ± 9.35 cumulative exposure days to FVIII).
Four patients were managed with differences from current guidelines1-3: first, the woman with type 2B VWD was treated with two drug-eluting stents whereas bare-metal stents are recommended. Dual antiplatelet therapy was then initiated but stopped at one month because of microcytic anemia. She was then treated with acid acetylsalicylic, 160mg per day instead of 75mg, and presented a severe gastrointestinal bleeding. Second, the patient with HB (FIX 34%) received no replacement therapy during PCI and no proton pump inhibitors while treated by antiplatelet drug, but he experienced no bleeding. Third, a HA patient (FVIII 6%) had a trough level of FVIII slightly lower than recommended (FVIII 37% versus > 50%) at day 7 after CABG. He presented a hemopericardium the next day, complicated with cardiac tamponade. Lastly, a moderate HA patient had no long-term antiplatelet therapy after CABG. However, he did not experience any new cardiovascular event during the following 4 years.
During the follow-up (median: 24,5 months), only one HA (FVIII 20%) patient had a new cardiovascular event: a critical lower limb ischemia complicated with an arterial ulcer at the age of 91 years, 11 years after CABG. In contrast, 3 patients experienced a severe bleeding while treated by dual or low-dose aspirin: one hemopericardium, one gastrointestinal bleeding and one intracranial bleeding at J7 post-CABG, 13 months and 11 years after the cardiac event, respectively.
Conclusion: This series of 8 patients confirms the significant risk of severe bleeding complications when antiplatelet drug is initiated in patients with hemophilia or VWD. In 1/3 cases, the severe bleeding occurred despite strict adherence to current recommendations.
No relevant conflicts of interest to declare.
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