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The most frequent haematological malignancy associated with acquired hypo/dysfibrinogenemia is multiple myeloma. We present an unusual case of severe haemorrhagic diathesis due to acquired hypofibrinogenemia in a patient with early T-cell precursor acute lymphoblastic leukaemia/lymphoma (ETP-ALL/LBL). A 57-year-old male was admitted to the General Internal Medicine Department of Padova University Hospital for acute massive haematomas of the left lower extremity associated with macrohaematuria. Coagulation tests showed prolonged prothrombin time, activated partial thromboplastin time and thrombin time due to isolated severe hypofibrinogenemia (antigen 0.70 g/L and activity 26%). The radiological workup showed a bulky lesion located in the anterior mediastinum, and a biopsy led to the diagnosis of ETP-ALL/LBL. Fibrinogen replacement therapy failed to correct the bleeding diathesis and we were able to exclude other frequent causes of acquired hypofibrinogenemia (i.e., liver dysfunction, fibrinogen-specific antibody or drug toxicity); therefore, we hypothesised that hypofibrinogenemia might stem either from enhanced removal of fibrinogen from the circulation or consumptive coagulopathy. Notably, only after initiating a specific chemotherapy treatment did the patient start showing improvement in bleeding symptoms and achieve normal fibrinogen levels.

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Epstein-Barr virus is a widely spread Herpesvirus. Primary EBV infection affects children and young people, inducing haematological changes, with lymphocytosis being the most common. Moderate symptomless thrombocytopenia is found in 50% of the patients, however, severe thrombocytopenia is exceptionally rare. We present a case report of a 20-year-old man with an acute EBV infection, severe thrombocytopenia, and no signs of infectious mononucleosis.

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While coronavirus disease 2019 (COVID-19) primarily affects the respiratory tract, pathophysiological changes of the cardiovascular system remain to be elucidated. We performed a retrospective cardiopathological analysis of the heart and vasculature from 23 autopsies of COVID-19 patients, comparing the findings with control tissue. Myocardium from autopsies of COVID-19 patients was categorised into severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) positive (n = 14) or negative (n = 9) based on the presence of viral RNA as determined by reverse transcriptase polymerase chain reaction (RT-PCR). Control tissue was selected from autopsies without COVID-19 (n = 10) with similar clinical sequelae. Histological characteristics were scored by ordinal and/or categorical grading. Five RT-PCR-positive cases underwent in situ hybridisation (ISH) for SARS-CoV-2. Patients with lethal COVID-19 infection were mostly male (78%) and had a high incidence of hypertension (91%), coronary artery disease (61%), and diabetes mellitus (48%). Patients with positive myocardial RT-PCR died earlier after hospital admission (5 versus 12 days, p < 0.001) than patients with negative RT-PCR. An increased severity of fibrin deposition, capillary dilatation, and microhaemorrhage was observed in RT-PCR-positive myocardium than in negatives and controls, with a positive correlation amongst these factors All cases with increased cardioinflammatory infiltrate, without myocyte necrosis (n = 4) or with myocarditis (n = 1), were RT-PCR negative. ISH revealed positivity of viral RNA in interstitial cells. Myocardial capillary dilatation, fibrin deposition, and microhaemorrhage may be the histomorphological correlate of COVID-19-associated coagulopathy. Increased cardioinflammation including one case of myocarditis was only detected in RT-PCR-negative hearts with significantly longer hospitalisation time. This may imply a secondary immunological response warranting further characterisation.

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INTRODUCTION: Autoimmune factor XIII (FXIII) deficiency (AiF13D) due to anti-FXIII autoantibodies is an extremely rare, life-threatening bleeding disorder that mostly occurs in the elderly. The number of patients diagnosed with AiF13D has been increasing in Japan, probably because of the nationwide survey on AiF13D supported by the Japanese Ministry of Health, Labour and Welfare. AIM: To explore the pathologic characteristics of coagulation parameters in AiF13D. METHODS: AiF13D-suspected cases were consulted, and underwent unified/integrated coagulation screening and were definitively diagnosed as AiF13D separately. RESULTS: AiF13D patients had lower FXIII antigen levels than non-AiF13D patients, but their values overlapped. Among a series of 22-item screening tests and their resulting parameters, the 'FXIII inhibitory potential' yielded by a 1:1 mixing test of the patient's and healthy control's plasma and its 'residual FXIII activity' in 54 AiF13D cases were most distinguishable from 139 non-AiF13D cases, followed by FXIII activity per se and FXIII-specific activity. While the cross-linked α2 -plasmin inhibitor level reduced, the levels of D-dimer, fibrin/fibrinogen degradation products and plasmin-plasmin inhibitor complex increased, probably because the patients' haematoma nonspecifically induced secondary fibrinolysis in both AiF13D and non-AiF13D patients. CONCLUSION: AiF13D appears to induce a hypocoagulopathy combined with a hyper-fibrinolytic state secondary to severe FXIII deficiency caused by anti-FXIII autoantibodies, and the consequent bleeding further modifies its pathological conditions. In addition, the 1:1 mixing test of FXIII activity was confirmed to be a reliable screening method for AiF13D, especially when its derivative parameter, such as the 'FXIII inhibitory potential' or 'FXIII inhibitory potential ratio', is employed.

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BACKGROUND: Bovine neonatal pancytopenia (BNP) is a haemorrhagic disease of neonatal calves. BNP was first described in Germany in 2009, later on also in other European countries, and in New Zealand in 2011. The disease is characterised by spontaneous bleeding, pancytopaenia in the bone marrow, and a high case fatality ratio. The causal role of a specific bovine viral diarrhoea virus (BVDV) vaccine (PregSure®BVD, then Pfizer Animal Health, now Zoetis, Berlin, Germany) has been established over the last years, causing the production of alloantibodies in some vaccinated cattle, which in the case of pregnant cattle, are transferred to the newborn calf via the colostrum. However, striking regional differences in the incidence of the disease were observed within Germany and other countries, but as the disease was not notifiable, no representative data on the spatial distribution are available. In this study, we address the spatial distribution and incidence of BNP using the results of two representative surveys amongst cattle practitioners in Bavaria, Germany. The surveys, asking about the occurrence of BNP, were conducted in 2009 and 2010. Answers were analysed spatially by testing for clusters using space-time models. Practitioners were also asked how many cows they serve in their practice and this number was used to estimate the incidence of BNP. Furthermore, in the survey of 2010, practitioners were also asked about usage of vaccine against BVDV. RESULTS: From the results of the surveys, three clusters were identified in Bavaria. These clusters also coincided with the usage of the specific BVDV vaccine as indicated by the veterinary practices. Furthermore, the representative surveys allow the estimation of the incidence of BNP to be in the order of 4 cases per 10,000 calves at risk. CONCLUSIONS: The study is the only representative survey conducted on BNP. Despite the fact that BNP is a non-infectious disease, regional clusters were identified.

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CASE HISTORY: Cases were obtained through passive surveillance reporting by veterinary pathologists, via the Ministry for Primary Industries Exotic Pest and Disease Hotline. They included ill or dead cows that had evidence of frank haemorrhage, petechial haemorrhages on mucous membranes, wasting or dermatitis of unknown cause, and were reported between 2009-2014. Affected cows (n=16) were from nine seasonally calving dairy farms, aged ≥3 years, and were predominantly in their mid-to-late non-lactating period. A brassica crop was identified in 15/16 cases as part of the current or recent ration. CLINICAL FINDINGS: Eight cows were found dead or died within 2 days of first signs. In eight cases death or euthanasia took place up to 3 weeks after signs were first observed. Cattle clinically examined prior to death (n=11) were generally inappetant, and recumbent or reluctant to move. Five cases had pale mucous membranes, three had petechiae and two were jaundiced. Rectal temperature was normal to sub-normal in eight cases. Evidence of melena or fresh blood at the anus or mouth was found in five cases. In three cases, alopecia and skin thickening was present, predominantly affecting the head and neck. PATHOLOGICAL FINDINGS: Petechiation of mucosal and internal serosal membranes, myocardium, subcutis and skeletal muscle was found in 10 cases. Frank haemorrhage was present in six cases, including haematomas of the subcutis, skeletal musculature, mesentery or omentum, and lumenal haemorrhage of the abomasum and/or intestine. In five cases pale nodules within myocardium and/or kidney, liver or spleen were present. Histopathologically, these were confirmed as granulomatous inflammatory lesions, which were also present within a wide range of tissues. Granulomatous foci typically comprised aggregates of macrophages, lymphocytes, plasma cells, prominent multinucleated giant cells and eosinophils. DIAGNOSIS: Idiopathic multisystemic granulomatous and haemorrhagic disease, occurring sporadically in dairy cattle, in the absence of feeds or feed additives previously associated with comparable syndromes. CLINICAL RELEVANCE: This is the first description of a novel systemic granulomatous and haemorrhagic syndrome seen in adult dairy cattle most often in their non-lactating period. The presentation can mimic important exotic disease differentials in New Zealand including anthrax, haemorrhagic septicaemia (associated with selected Pasteurella multocida strains) or infection with bovine viral diarrhoea virus type 2.

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BACKGROUND: Several research groups from different European countries have worked on the aetiopathogenesis of bovine neonatal pancytopenia (BNP) and an association between the use of the vaccine PregSure BVD (Pfizer, Germany) and the development of this haemorrhagic disease was confirmed. Because BNP is not a notifiable disease, it is difficult to obtain information on its incidence. Based on pharmacovigilance (PhV) data, which are the only officially available data at the national level, the incidence of BNP is considered low. However, voluntary reporting of the disease can lead to underreporting. To gain more insight into the incidence of BNP among the affected herds, an epidemiological study was performed, which focused on 243 farms in Germany with cases of BNP. Farmers were asked to report the occurrence of BNP, including the number of cases, which allowed calculation of incidence in the affected herds. Matching such data with the registered cases in the National PhV System (NPhVS) gave us an opportunity to assess the extent of BNP underreporting. RESULTS: On 243 farms, a total of 1195 calves younger than 4 weeks with haemorrhagic diathesis were registered. In 58 % of the reports, a diagnosis of BNP was confirmed by blood analysis and or by necropsy. The number of cases observed on individual farms ranged from 1 to 80. Based on these results, the incidence of BNP on affected farms ranged from 0.3 to 15.2 % (median 2.9 %). The maximal incidence in the year with the highest number of BNP calves ranged between 0.4 and 18.6 % (median 3.3 %). Comparing the number of cases registered in the NPhVS to the numbers found in this study revealed considerable underreporting to the national database: only 44 % of the farms and 41 % of the BNP calves included in the study were registered in the NPhVS. CONCLUSIONS: In spite of the opportunity to report BNP calves to the Paul-Ehrlich-Institut (Langen, Germany), the estimated number of undetected BNP cases is remarkably high. However, even if the revealed substantial underreporting is taken into account, the incidence of BNP is low. Nevertheless, the incidence on some affected farms is very high, resulting in considerable financial losses that should not be underestimated. Although the exact pathomechanism of BNP at the molecular level is still not known, its incidence is clearly declining following withdrawal of PregSure BVD from the market.

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Mycoplasma suis causes infectious anaemia in pigs (IAP), which can manifest in various degrees of severity depending on the virulence and the host's susceptibility. As M. suis cannot be cultured in vitro experimental infections of splenectomised animals play an essential role for pathogenesis research. The aim of the present study was to characterise the course of experimental infection using the highly virulent and red blood cell (RBC-) invasive M. suis strain KI3806, to compare the experimental course in splenectomised and non-splenectomised pigs and to correlate clinical and haematological parameters with M. suis blood loads. All infected splenectomised pigs (n=7) were PCR-positive 2 days post infection (DPI) with maximum mean bacterial loads of 1.61 × 10(10)M. suis/mL on 8 DPI. They developed severe anaemia and massive hypoglycaemia by 8 DPI and had to be euthanised preterm (until 8 DPI) without seroconversion. The non-splenectomised pigs (n=7) became PCR-positive within 23 DPI and reached a maximum mean M. suis load of 1.64 × 10(5)M. suis/mL on 8 DPI. They developed mild anaemia, massive skin alterations with petechiae and haemorrhagic diathesis and seroconverted within 35 DPI. The study demonstrated that experimental infection of splenectomised pigs with the highly virulent M. suis strain KI3806 induces a fulminant course of infection. In contrast, M. suis strain KI3806 induces a mild course of disease in non-splenectomised pigs, which resembles the situation in naturally infected pigs. Therefore, these infection models are valuable for future pathogenesis studies on acute and chronic M. suis infections.

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