A case of late onset of primary antiphospholipid syndrome

PurposeAntiphospholipid syndrome (APS) usually affects young patients and is rarely described in the elderly. Here, we present a case of late-onset of triple-positive primary APS characterized by recurrent thrombotic events.MethodsIn November 2019, an 80-year-old man presented the first deep vein thrombosis in his left leg. He received fondaparinux treatment for one year, but the thrombosis relapsed one month after stopping treatment. The search for thrombophilic causes has shown positivity for antiphospholipid antibodies (LAC, anticardiolipin, and anti-beta2 glycoprotein I IgM at high titres). In addition, the patient underwent first-level diagnostics and endoscopic examinations excluding other immunological causes, infections and malignancy. A diagnosis of primary APS was made and the warfarin therapy started with a range of INR between 2 and 3. In November 2021, the patient was brought to our attention following the recurrence of thrombosis of the deep iliac and femoral veins despite anticoagulant treatment. Laboratory tests confirmed the presence of triple high titre positivity of antiphospholipid antibodies and a total body CT scan confirmed the absence of suspected malignant lesions. Serological studies with a comprehensive autoimmunity panel for other autoimmune disorders were negative and an echocardiographic study ruled out the presence of cardiac involvement.ResultsAlthough age has been demonstrated to be a risk factor for severe bleeding episodes in patients placed on long-term anticoagulation, we decided to start hydroxychloroquine and combination therapy with warfarin (INR range between 2.5 and 3.5) and low-dose aspirin according to EULAR recommendations, considering the patient’s good clinical condition and absence of comorbidities. The patient was informed about the nature of the disease and the need for treatment with a high risk of bleeding. In December 2021, despite vaccination with two doses, he contracted COVID-19 infection and warfarin treatment was replaced with low molecular weight heparin at prophylactic dosage, but after some days he presented dyspnoea with desaturation. A lung CT scan showed bilateral pulmonary embolism, attributable to intercurrent viral infection and to APS (not completely controlled after warfarin withdrawal), and so clinicians decided to replace treatment with warfarin. After one month, patient had been discharged from hospital in good clinical health.ConclusionsAccurate diagnosis and treatment of late-onset APS represent a challenge due to the lack of knowledge of this disease in the elderly.

AN UNUSUAL ASSOCIATION between THROMBOTIC THROMBOCYTOPENIC PURPURA and PRIMARY ANTIPHOSPHOLIPID SYNDROME

Background: Thrombotic thrombocytopenic purpura (TTP) is a rare and life-threatening thrombotic microangiopathy characterized by microangio-pathic haemolytic anemia, consumption thrombocytopenia and organ injury, particularly kidney failure and neurological manifestation1. Two forms are distinguished: the hereditary one, caused by a deficit of the metallopro-tease ADAMTS13, and the idiopathic one characterized by the presence of antibodies directed against ADAMTS13. The second one is the most common. There are various subgroups of acquired TTP associated with HIV infection, sepsis, pregnancy, autoimmune disease, disseminated malignancies and drugs. Antiphospholipid syndrome (APS) is a clinical immunological condition characterized by thromboembolic events, repe-tead miscarriages or stillbirth and thrombocytopenia;it can be a primary disorder or due to connective tissue disease, in particular systemic lupus erythematosus2. Objectives: We describe a case of TTP associated with a primary APS. The real clinical challenge lies in the differential diagnosis between TTP and anti-phos-pholipid antibody syndrome. Methods: A 37-year-old man presented to the emergency department for short-term episodes of anesthesia of the right upper limb and face with spontaneous resolution. In his past medical history, he suffered of antiphospholipid syndrome treated with warfarin. Upon admission, blood tests revealed severe thrombocytopenia, haemolytic anemia with schistocytes on peripheral blood smear, low thrombin time and prolongation in the prothrombin time. Neurological symptoms were assessed by electroencephalogram and CT brain, resulted negative, while a brain MRI revealed acute-subacute ischemic stroke. Based on these fndings we suspected a diagnosis of TTP, subsequently confrmed by reduced activity of ADAMTS-13 with borderline ADAMTS-13 inhibitory antibodies. Immunological testing confrmed positivity of antiphospholipid antibodies and antinuclear antibodies. Results: According to the last guidelines3 about management of acute episode of TTP, immediate therapy with high-dose corticosteroids (prednisone 1 mg/kg) and plasmapheresis was started and then we added infusion of ritux-imab (375 mg/m2/week for 4 times). Efficacy of treatment was evaluated by weekly dosage of ADAMTS13 activity, with a gradual rise in values (3 → 78%) and improvement in symptoms and laboratory examination. After persistent remission, we gradually reduced steroid therapy. Few months later, in February 2021, patient developed a bilateral comunitary pneumonia, that required hospitalization, oxygen-therapy (also with C-PAP) and endovenous antibiotics. After two weeks patient was discharged from hospital in good clinical health and he was subjected to periodic outpatients visits. Disease activity was in remission, so steroid therapy was reduced and recently we added hydroxychloroquine for APS. Some days ago patient developed covid-19 infection, despite vaccination, and he was treated with monoclonal antibodies, with good clinical response. Conclusion: We have described a rare clinical case of TTP, despite concomitant warfarin treatment for primary anti-phospholipid syndrome. A careful follow-up of these medical conditions is recommended for patient's fragility and for the risk of related serious clinical complications.

Unexplained pulmonary embolism post SARS-CoV2 pneumonia in a patient with MYH9-related disease: a case report

This report describes the case of a man affected by Myosin Heavy Chain 9 (MYH9)-related platelet disorder, with a recent history of SARS-CoV-2 pneumonia, who developed pulmonary embolism (PE). At the admittance the patient presented a marked thrombocytopenia. The rotational thromboelastometry (ROTEM) showed a reduction in maximum clot firmness. The CT scan showed a lobar PE while and no sign of superficial or deep venous thrombosis was found. Given the contraindication of anticoagulant therapy due to severe thrombocytopenia, after collegial evaluation of the case, an inferior vena cava filter was applied. The patient was discharged after 5 days of hospitalization, and fondaparinux 2.5 mg subcutaneously was prescribed for two months. Could MYH9 mutation contribute to thrombotic predisposition? Or rather the endothelial dysfunction induced by SARS-CoV-2 infection? The report presents a dissertation on the possible causes for the PE and describes the therapeutic strategy adopted. (www.actabiomedica.it).

Incidence and outcomes of subclinical atrial fibrillation in a cohort of moderate-severe CoViD-19 admitted in a subintensive Internal Medicine unit

Background and Aims: Subclinical atrial fibrillation (SCAF) is an asymptomatic, short and fast atrial arrhythmia observed during long-term monitoring. SCAF incidence ranges between 5-15% in critical illness and is associated to an increased risk of one-yeardeath, while its role in thromboembolism is debated. With this pilot study, we assessed SCAF incidence in a longitudinal cohort of moderate-to-severe CoViD-19, evaluating its association with inhospital death, major bleeding or thromboembolism. Methods: We considered all the subjects admitted to our subintensive medicine department for moderate-to-severe CoViD-19 undergoing to continuous ECG monitoring for at least seven consecutive days, evaluating the occurrence of SCAF daily. We also collected history, ECG, age, sex, occurrence of in-hospital death, thromboembolism and major bleeding. Results: Of 34 consecutive patients, 4 were excluded for pre-existing atrial fibrillation. We analysed 30 subjects who completed ECG monitoring: mean age was 66±14.8 years, 47% were females. SCAF incidence was 20% in 7 days. During the admission we observed 6(20%) deaths, 2(6%) thromboembolic events and 2(6%) major bleedings, with no relationship with SCAF occurrence. SCAF was more frequently observed in severe than in moderate CoViD-19 (p=0.0001). Conclusions: SCAF shows high incidence in CoViD-19, especially within a severe disease. This pilot study did not underline an association with short-term events: we are expanding our cohort and performing a longer follow-up to validate our data and to assess associations with post-CoViD events.

Determinants of subclinical atrial fibrillation in a cohort of moderate-to-severe CoViD19

Background and Aims: Subclinical atrial fibrillation (SCAF) is defined as a fast, asymptomatic and self-terminating arrhythmic event, often diagnosed by long-term monitoring. We observed a high SCAF prevalence in moderate-to-severe CoViD-19. We aimed to assess the determinants of SCAF in this cohort. Methods: All the consecutive patients affected by moderate-tosevere CoViD-19 admitted in a subintensive CoViD-19 unit were enrolled;each patient was submitted to continuous ECG monitoring for 7 days;for each subject, we collected - at the admission - age, sex, BMI, history of heart failure, history of hypertension, history of COPD, LUSS score, 12-leads ECG (calculating intervals and assessing the most common alterations), BNP, Troponin I and PaO2/FiO2. Results: We obtained 34 consecutive patients;4 patients were excluded for pre-existing atrial fibrillation;SCAF was observed in 20% of the sample;age, sex, BMI, history of heart failure, hypertension and COPD, all the ECG intervals (PR, QRS and ST), ECG alterations (atrioventricular blocks, intraventricular blocks, hypertrophy or ischemia), BNP, Troponin I and PaO2/FiO2 did not result statistically associated with SCAF. Patient developing SCAF had a higher LUSS score resulted significantly associated to SCAF (LUSS in no-SCAF: 15.36±5,38;LUSS in SCAF: 20,0±4,27;p=0,027), even after Bonferroni correction. Conclusions: SCAF has a high prevalence in CoViD-19 and seems to be correlated more to the disease severity than to the classical risk factors for atrial fibrillation. Larger cohorts are required to validate our observations.