A case of acquired factor XIII deficiency secondary to plasmablastic lymphoma

Acquired factor XIII (FXIII) deficiency is an extremely rare and potentially fatal bleeding disorder. Immune-mediated FXIII deficiency is due to the development of anti-FXIII autoantibodies which may develop with concomitant conditions that cause immune dysregulation such as malignancies or autoimmune disorders. Clinical presentation includes delayed post-operative bleeding or spontaneous soft tissue hematomas and/or cerebral bleeding. Since screening coagulation laboratory tests (prothrombin time, activated partial thromboplastin time, and fibrinogen) are typically normal, acquired FXIII deficiency is likely to be overlooked and underdiagnosed. The management of immune-mediated FXIII deficiency is based on hemostatic therapy, autoantibody removal and eradication of the underlying etiology; however, no treatment guidelines are still available. Here we report a case of acquired FXIII deficiency associated with plasmablastic lymphoma, in order to raise awareness of this rare bleeding disorder and consent prompt life-saving management

Safety of COVID-19 mRNA vaccination in patients with history of acquired hemophilia A: a case series

Coronavirus disease 2019 (COVID-19) following severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection called for a specific and massive vaccination campaign. Acquired hemophilia A (AHA) is a potential life-threatening coagulopathy. Hematological- targeted autoimmune conditions including immune thrombocytopenia, vaccine-induced thrombotic thrombocytopenia and AHA emerged during large-scale vaccination against SARS-CoV-2 and contributed to vaccination hesitation. The aim of the present study was to evaluate the putative recurrence of AHA after vaccination against SARS-CoV-2 with mRNA vaccines (BNT162b2 and mRNA- 1273) in patients with relatively recent history of AHA. Thirteen patients (8 women and 5 men, mean age = 63.1±16.6 years) with AHA in the previous two-to-five years were enrolled in the study. Platelet count, prothrombin time (PT), partial thromboplastin time (PTT), fibrinogen and Factor VIII levels were evaluated 48 hours prior to each vaccine dose and 10 days post-vaccination. Clinical self-assessment and remote video visits were performed in the presence of even minor hemorrhagic signs. No major bleeding events were detected at any time-point, including evaluation at 30 days after the 3rd vaccine dose. No significant hemorrhagic changes were observed, in particular no thrombocytopenia and/or significant alterations in PTT and Factor VIII emerged across subjects. Patients with a previous history of AHA of various etiology do not seem to have an increased recurrence risk after a COVID-19 vaccination course of 3 doses with either mRNA vaccine. This finding supports this specific safety aspect in the face of the possible continuation of the vaccination campaign based on the trend of the COVID-19 pandemic

Carriers of ADAMTS13 Rare Variants Are at High Risk of Life-Threatening COVID-19

Thrombosis of small and large vessels is reported as a key player in COVID-19 severity. However, host genetic determinants of this susceptibility are still unclear. Congenital Thrombotic Thrombocytopenic Purpura is a severe autosomal recessive disorder characterized by uncleaved ultra-large vWF and thrombotic microangiopathy, frequently triggered by infections. Carriers are reported to be asymptomatic. Exome analysis of about 3000 SARS-CoV-2 infected subjects of different severities, belonging to the GEN-COVID cohort, revealed the specific role of vWF cleaving enzyme ADAMTS13 (A disintegrin-like and metalloprotease with thrombospondin type 1 motif, 13). We report here that ultra-rare variants in a heterozygous state lead to a rare form of COVID-19 characterized by hyper-inflammation signs, which segregates in families as an autosomal dominant disorder conditioned by SARS-CoV-2 infection, sex, and age. This has clinical relevance due to the availability of drugs such as Caplacizumab, which inhibits vWF-platelet interaction, and Crizanlizumab, which, by inhibiting P-selectin binding to its ligands, prevents leukocyte recruitment and platelet aggregation at the site of vascular damage

New generation analysis of thrombin generation in retinal vein thrombosis

Purpose To investigate potential mechanisms involved in retinal vein occlusion (RVO) we evaluated thrombin generation and soluble CD40 ligand (sCD40L) with respect to other known thrombophilic factors. Methods 68 patients affected by RVO (28 central, 40 branch) and 60 healthy controls were evaluated for endogenous thrombin potential (ETP) by a chromogenic method and sCD40L by ELISA technique. Polymerase chain reaction (PCR) was employed for genetic polymorphisms and coagulative/chromogenic methods for othe coagulation factors. Results Independently of genetic polymorphisms ETP was increased in patients with CRVO whereas sCD40L was higher in the whole cohort. Conclusions Our data indicate an involvement of global coagulative activation in CRVO patients as suggested by ETP

A cohort mortality study of leather tanners in Tuscany, Italy

Background Work in leather tanning may involve exposure to a wide range of chemicals. Some of these are carcinogens or suspected carcinogens. Increased risk for a number of cancers have been reported, although there are considerable inconsistencies between studies. The present study investigates the mortality of leather tanners in Tuscany, Italy. Methods Tanneries were selected from the 1996 Valdarno Inferiore Tanneries Census and were in operation since December 31, 1970. Employees were followed until December 31, 1998 through company records, and the National and Regional Death Index. Demographic and work history data were abstracted from company payrolls. Regional mortality rates were used to calculate Standardized Mortality Ratio (SMR). Analyses were completed for the overall cohort (men and women) and for men who ever worked as of finisher chrome tanners, and vegetable tanner (only men). Results The cohort consisted of 4,874 workers (4,150 males and 724 females) employed in 92 tanneries active in 1996 and operating on December 31, 1970. Ascertainment of vital status and cause of death were completed for all individuals by the end of follow-up, December 31, 1998. Males showed increases for cancer of the endocrine glands (SMR 5.67, 4 observed (obs), 90% Confidence Intervals (Cl) 195-1,308), blood diseases (SMR 3.29, 4 obs, 90% CI 112-753), mental disorders (SMR 1.95, 6 obs, 90% Cl 85-385), violence and accidents (SMR 1.30, 54 obs, 90% CI 102-163). Mortality from myeloid leukemia was increased in males (SMR 2.08, 5 obs, 90% CI 82-437) and in females (SMR 5.99, 2 obs, 90% CI 106-1,887). One death from nasal cancer was observed versus 0.2 expected. Mortality from lung cancer was increased among finishers (SMR 1.45, 19 obs, 90% CI 95-212), an increase was observed also for bladder cancer (SMR 1.25, 2 obs, 90% CI 22-393) and pancreatic cancer (SMR 1.20, 2 obs, 90% CI 21-379). Conclusions The study confirms previous observations among tanners of increased mortality from lung, bladder, and pancreatic cancer. Noteworthy are the increased mortality from myeloid leukemia together with the new findings of an increased mortality from endocrine glands tumors, blood diseases, and psychiatric disorders which should be considered with caution because of the small number of cases and the novelty of the observation