Anemia is extremely common in hospitalized patients who are old and often with multiple diseases. We evaluated 435 consecutive patients admitted in the internal medicine department of a hub hospital and 191 (43.9%) of them were anemic. Demographic, historic and clinical data, laboratory tests, duration of hospitalization, re-admission at 30 days and death were recorded. Patients were stratified by age (80 years), anemia severity, and etiology of anemia. The causes of anemia were: iron deficiency in 28 patients, vitamin B₁₂ and folic acid deficiencies in 6, chronic inflammatory diseases in 80, chronic kidney disease in 15, and multifactorial in 62. The severity of the clinical picture at admission was significantly worse (p < 0.001), length of hospitalization was longer (p < 0.001) and inversely correlated to the Hb concentration, re-admissions and deaths were more frequent (p 0.017) in anemic compared to non-anemic patients. A specific treatment for anemia was used in 99 patients (36.6%) (transfusions, erythropoietin, iron, vitamin B₁₂ and/or folic acid). Anemia (and/or its treatment) was red in the discharge letter only 54 patients. Even if anemia is common, in internal medicine departments scarce attention is paid to it, as it is generally considered a “minor” problem, particularly in older patients often affected by multiple pathologies. Our data indicate the need of renewed medical attention to anemia, as it may positively affect the outcome of several concurrent medical conditions and the multidimensional loss of function in older hospitalized patients.

Little information is available on the beneficial effects of cholecalciferol treatment in comorbid patients hospitalized for COVID-19. The aim of this study was to retrospectively examine the clinical outcome of patients receiving in-hospital high-dose bolus cholecalciferol. Patients with a positive diagnosis of SARS-CoV-2 and overt COVID-19, hospitalized from 15 March to 20 April 2020, were considered. Based on clinical characteristics, they were supplemented (or not) with 400,000 IU bolus oral cholecalciferol (200,000 IU administered in two consecutive days) and the composite outcome (transfer to intensive care unit; ICU and/or death) was recorded. Ninety-one patients (aged 74 ± 13 years) with COVID-19 were included in this retrospective study. Fifty (54.9%) patients presented with two or more comorbid diseases. Based on the decision of the referring physician, 36 (39.6%) patients were treated with vitamin D. Receiver operating characteristic curve analysis revealed a significant predictive power of the four variables: (a) low (<50 nmol/L) 25(OH) vitamin D levels, (b) current cigarette smoking, (c) elevated D-dimer levels (d) and the presence of comorbid diseases, to explain the decision to administer vitamin D (area under the curve = 0.77, 95% CI: 0.67–0.87, p < 0.0001). Over the follow-up period (14 ± 10 days), 27 (29.7%) patients were transferred to the ICU and 22 (24.2%) died (16 prior to ICU and six in ICU). Overall, 43 (47.3%) patients experienced the combined endpoint of transfer to ICU and/or death. Logistic regression analyses revealed that the comorbidity burden significantly modified the effect of vitamin D treatment on the study outcome, both in crude (p = 0.033) and propensity score-adjusted analyses (p = 0.039), so the positive effect of high-dose cholecalciferol on the combined endpoint was significantly amplified with increasing comorbidity burden. This hypothesis-generating study warrants the formal evaluation (i.e., clinical trial) of the potential benefit that cholecalciferol can offer in these comorbid COVID-19 patients.

In Italy, a significant proportion of patients with autosomal dominant inheritance of macrothrombocytopenia have been recognized as having heterozygous Bernard-Soulier syndrome carrying the Bolzano-type defect. This condition prompted a systematic review of our out-patients with chronic isolated macrothrombocytopenia. We recognized that the affected members of two unrelated families represented a new variant of heterozygous Bernard-Soulier Syndrome with autosomal dominant inheritance. Sequencing analysis of the GPIbα gene revealed a novel heterozygous mutation, A169C, resulting in an N41H substitution in the protein. This aminoacid belongs to the first leucine-rich repeat of the chain. The molecular modeling suggests that the replacement of the N41 with a histidine (N41H) drastically disturbs the structure of the first portion of GPIbα N-terminal, directly involved in von Willebrand factor binding. As a consequence, platelet aggregation to 1.2 mg/mL of ristocetin is slightly impaired and flow cytometry reveals a reduced binding of monoclonals directed against N-terminal epitopes of the GPIbα.

Fabris F, Luzzatto G, Soini B, Ramon R, Scandellari R, Randi ML, Girolami A (University of Padua Medical School, Padova, Italy). Risk factors for thrombosis in patients with immune mediated heparin‐induced thrombocytopenia. J Intern Med 2002; 252: 149–154. Background. As reported by major clinical series in the literature, about 2% of patients receiving unfractionated heparin (UFH) develop immune‐mediated (type II) heparin‐induced thrombocytopenia (HIT) that may be complicated in 30–75% of cases by a paradoxical thrombotic syndrome (HITTS), either arterial or venous. HITTS carries relevant rates of mortality and morbidity, amongst which cerebral and/or myocardial infarction and limb amputations. It is unclear as yet why some patients suffer from isolated thrombocytopenia (HIT), whilst others have HITTS. The aim of the present study was to look for clinical and laboratory features related to the occurrence of HITTS. Patients and methods. We retrospectively analysed the clinical records of 56 patients with proven HIT, as diagnosed on clinical grounds and by in vitro demonstration of immunoglobulin (IgG)/IgM against the PF4/heparin complex. Thirty‐four patients (61%) had HITTS (19 venous thrombosis, seven arterial thrombosis, five arterial and venous thrombosis, two skin necrosis, one diffuse intravascular coagulation), whereas 22 had uncomplicated HIT. Amongst HITTS patients, two had limb amputation, five had recurrent thrombosis and seven died. Amongst HIT patients three died from causes unrelated to HIT. Results. No significant difference in sex, age, previous exposure to heparin, UFH route of administration or dose, duration of therapy, time of onset of thrombocytopenia and platelet count recovery, nor antiheparin/PF4 antibodies subtype (IgG or IgM) was detected when comparing HIT and HITTS. In contrast, in the HITTS group a higher prevalence of orthopaedic surgery (15 of 34 vs. 2/22; P=0.01), a significantly lower platelet count nadir (43 ± 32 vs. 75 ± 63 × 10⁹/L; P=0.01) and a significantly higher titre of antiheparin/PF4 antibodies, expressed as optical density of enzyme‐linked immunosorbent assay (ELISA); (1989 ± 1024 vs. 1277 ± 858; P=0.009), were observed in comparison with the HIT group. Amongst HITTS patients, the prevalence of venous thrombosis was significantly higher in orthopaedic patients and in those being treated for venous thromboembolism (18/24 vs. 1/9 patients, χ² 8.4, P=0.004), whilst arterial thrombosis (ART) occurred more often in heparin treatment for arterial disease (3/4 vs. 4/29 patients, χ² 4.6, P=0.03). Conclusions. Orthopaedic surgery, the severity of thrombocytopenia and high antiheparin/PF4 antibodies titre are adverse prognostic or concurrent factors in the development of HITTS.

There were 50 consecutive idiopathic thrombocytopenic purpura (ITP) adult patients (platelet count < 100 × 109/L) grouped according to positivity or negativity of a solid-phase modified antigen capture enzyme-linked immunosorbent assay (ELISA) test (MACE) against glycoprotein IIb/IIIa (GPIIb/IIIa), Ib/IX, and IIa/IIIa. Observation started on the day of MACE assay and lasted at least 6 months. Clinical worsening was defined as the need for starting or modifying therapy because of thrombocytopenia lower than 20 × 109/L or patient admission due to bleeding symptoms. MACE-positive patients had a higher probability of clinical worsening than MACE-negatives (P < .004). The proportion of patients worsening was 18 (72%) of 25 among MACE-positives and 8 (32%) of 25 among MACE-negatives. The median time to clinical worsening was 2.1 months for MACE-positive patients and 27.7 months for MACE-negatives. The assay of specific platelet autoantibodies may be a useful prognostic tool for the clinical course of ITP. (Blood. 2004;103:4562-4564)

Heparin-induced thrombocytopenia (HIT) is caused by platelet activating antibodies that recognize platelet factor 4/heparin (PF4/H) complexes. Laboratory testing plays a key role in the diagnosis of HIT. As functional assays are unfeasible for most clinical laboratories, antigen binding assays are commonly used in routine testing. However, their low specificity leads to overdiagnosis of HIT. Therefore, it is advisable to improve screening tests in this setting.Blood samples from 114 patients in whom HIT was suspected were investigated using a chemiluminescence test (HemosILTwenty-nine (25.4%) out of 114 subjects with suspected HIT had a positive HIPA test. None of patients with a 4Ts score <4 were positive at HIPA. HemosILThe HemosIL