Background: Development and worldwide availability of safe and effective vaccines against severe ... more Background: Development and worldwide availability of safe and effective vaccines against severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) to fight severe symptoms of coronavirus disease 2019 (COVID-19) and block the pandemic have been a great achievement and stimulated researchers on understanding the efficacy and duration of different vaccine types.Methods: We investigated the levels of anti-SARS-CoV-2 antibodies (IgG) and neutralizing antibodies (NAbs) in 195 healthy adult subjects belonging to the staff of the University-Hospital of Ferrara (Italy) starting from 15 days up to 190 days (about 6 months) after the second dose of the BNT162b2 (Pfizer–BioNTech) mRNA-based vaccine (n = 128) or ChAdOx1 (AstraZeneca) adenovirus-based vaccine (n = 67) using a combined approach of serological and genomics investigations.Results: A strong correlation between IgG and NAb levels was detected during the 190 days of follow-up (r2 = 0.807; p < 0.0001) and was confirmed during the...
SARS-CoV-2 infection affects different organs and tissues, including the upper and lower airways,... more SARS-CoV-2 infection affects different organs and tissues, including the upper and lower airways, the lung, the gut, the olfactory system and the eye, which may represent one of the gates to the central nervous system. Key transcriptional factors, such as p53 and NF-kB and their reciprocal balance, are altered upon SARS-CoV-2 infection, as well as other key molecules such as the virus host cell entry mediator ACE2, member of the RAS-pathway. These changes are thought to play a central role in the impaired immune response, as well as in the massive cytokine release, the so-called cytokine storm that represents a hallmark of the most severe form of SARS-CoV-2 infection. Host genetics susceptibility is an additional key side to consider in a complex disease as COVID-19 characterized by such a wide range of clinical phenotypes. In this review, we underline some molecular mechanisms by which SARS-CoV-2 modulates p53 and NF-kB expression and activity in order to maximize viral replication...
The importance of host genetics and demography in coronavirus disease 2019 (COVID-19) is a crucia... more The importance of host genetics and demography in coronavirus disease 2019 (COVID-19) is a crucial aspect of infection, prognosis and associated case fatality rate. Individual genetic landscapes can contribute to understand Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) burden and can give information on how to fight virus spreading and the associated severe acute respiratory distress syndrome (ARDS). The spread and pathogenicity of the virus have become pandemic on specific geographic areas and ethnicities. Interestingly, SARS-CoV-2 firstly emerged in East Asia and next in Europe, where it has caused higher morbidity and mortality. This is a peculiar feature of SARS-CoV-2, different from past global viral infections (i.e., SARS-1 or MERS); it shares with the previous pandemics strong age- and sex-dependent gaps in the disease outcome. The observation that the severest COVID-19 patients are more likely to have a history of hypertension, diabetes and/or cardiovascular d...
In the last two decades, new insights have been gained regarding sex/gender-related differences i... more In the last two decades, new insights have been gained regarding sex/gender-related differences in cardiovascular disease (CVD). CVD represents the leading cause of death worldwide in both men and women, accounting for at least one-third of all deaths in women and half of deaths in women over 50 years in developing countries. Important sex-related differences in prevalence, presentation, management, and outcomes of different CVDs have been recently discovered, demonstrating sex/gender-specific pathophysiologic features in the presentation and prognosis of CVD in men and women. A large amount of evidence has highlighted the role of sex hormones in protecting women from CVDs, providing an advantage over men that is lost when women reach the menopause stage. This hormonal-dependent shift of sex-related CVD risk consequently affects the overall CVD epidemiology, particularly in light of the increasing trend of population aging. The benefits of physical activity have been recognized for ...
Despite convincing experimental evidence, epidemiological studies on the effects of serum uric ac... more Despite convincing experimental evidence, epidemiological studies on the effects of serum uric acid (SUA) on bone health are still conflicting since factors influencing SUA bioavailability have not been adequately considered. To shed some light on this issue, we investigated the impact of adiposity and menopause status on the relationship between SUA and bone health. We examined SUA in relation to bone mineral density (BMD) at different skeletal sites and with markers of bone metabolism in 124 pre-menopausal and 234 post-menopausal women and assessed whether adiposity, evaluated by anthropometry and dual x-ray absorptiometry (DXA), might have a discriminant role. After conservative adjustment (covariates: age, hormones treatment, smoking and time since menopause), SUA showed a significant and positive association with total hip BMD (β = 0.220, p < 0.01) among postmenopausal women, maintained also after adjustment for legs adiposity. Notably, stratification for waist circumference...
Abdominal adhesions (AA) account for the most common complication of peritoneal surgery with bowe... more Abdominal adhesions (AA) account for the most common complication of peritoneal surgery with bowel obstruction being the severest problem in the absence of effective predicting biomarkers. Anti-AA-barriers or adhesiolysis did not completely prevent bowel obstruction, although there is evidence they might reduce related complications requiring reoperation. In addition, gender-related predispositions have not been adequately investigated. We explored the role of coagulation Factor XIII (F13A1 and F13B subunit-genes) in patients following laparotomy, mostly median/lower median incision line. Globally, 426 patients (54%,♀), were PCR-SNP-genotyped for FXIIIA V34L (rs5985), FXIIIA P564L (rs5982), FXIIIA Y204F (rs3024477) and FXIIIB H95R (rs6003). Patients’ clinical phenotypes were: Group-A (n = 212), those who developed AA, and 55.2% of them developed bowel obstruction (subgroup-A1), the remaining were subgroup-A2; Group B (n = 214) were those who did not develop AA (subgroup-B1; 53.3%) o...
The effect of redox metals such as iron and copper on multiple sclerosis and amyotrophic lateral ... more The effect of redox metals such as iron and copper on multiple sclerosis and amyotrophic lateral sclerosis has been intensively studied. However, the origin of these disorders remains uncertain. This review article critically describes the physiology of redox metals that produce oxidative stress, which in turn leads to cascades of immunomodulatory alteration of neurons in multiple sclerosis and amyotrophic lateral sclerosis. Iron and copper overload has been well established in motor neurons of these diseases' lesions. On the other hand, the role of other metals like cadmium participating indirectly in the redox cascade of neurobiological mechanism is less studied. In the second part of this review, we focus on this less conspicuous correlation between cadmium as an inactive-redox metal and multiple sclerosis and amyotrophic lateral sclerosis, providing novel treatment modalities and approaches as future prospects.
Warfarin oral anticoagulant therapy (OAT) requires regular and frequent drug adjustment monitored... more Warfarin oral anticoagulant therapy (OAT) requires regular and frequent drug adjustment monitored by INR. Interindividual variability, drug and diet interferences, and genetics (VKORC1 and CYP2C9) make the maintenance/reaching of stable INR a not so easy task. HPLC assessment of warfarin/enantiomers was suggested as a valid monitoring-tool along with INR, but definite results are still lacking. We evaluated possible correlations between INR, warfarin/3'-hydroxywarfarin, and drug weekly dosage aimed at searching novel alternatives to OAT monitoring. VKORC1/CYP2C9 pharmacogenetics investigation was performed to account for the known influence on warfarin homeostasis. 133 OAT patients were recruited and assessed for warfarin/3'-hydroxywarfarin serum levels (HPLC), INR, and VKORC1 and CYP2C9 genotypes. A subgroup of 52 patients were monitored in detail (5 consecutive controls; c0-c4) till the target INR was reached. Correlation analyses were performed in both groups. In the whol...
SummaryAfter acute myocardial infarction (MI) the damaged heart has to be repaired. Factor XIII (... more SummaryAfter acute myocardial infarction (MI) the damaged heart has to be repaired. Factor XIII (FXIII) is considered a key molecule in promoting heart healing. FXIII deficiency was associated to cardiac rupture and anomalous remodelling in MI. During MI, FXIII contributes firstly to the intracoronary thrombus formation and shortly after to heal the myocardial lesion. To quantify the real contribution of FXIII in this process, and to explore its possible prognostic role, we monitored the FXIII-A subunit levels in 350 acute MI patients during the first six days (d0-d5) plus a control at 30–60 days (d30). A one-year follow-up was performed for all the patients. A transient drop in the FXIII-A mean level was noted in the whole cohort of patients (FXIII-Ad0 99.48 ± 30.5 vs FXIII-Ad5 76.51 ± 27.02; p< 0.0001). Interestingly, those who developed post-MI heart failure showed the highest drop (FXIII-Ad5 52.1 ± 25.2) and they already presented with low levels at recruitment. Similarly, th...
Annales françaises d'Oto-rhino-laryngologie et de Pathologie Cervico-faciale, 2012
This study is the first recognition of genetic implications (i.e. SNPs) in the field of sudden se... more This study is the first recognition of genetic implications (i.e. SNPs) in the field of sudden sensorineural hearing loss. In detail, SNPs of iron homeostasis genes seem to have a role in sudden sensorineural hearing loss establishment. Pharmacogenetics aspects have been discussed
1having factor VIII (FVIII) deficiency in common, albeit of different origin. In hemophilia A, th... more 1having factor VIII (FVIII) deficiency in common, albeit of different origin. In hemophilia A, the FVIII defect is associated with abnormalities in the FVIII gene, with an X-linked pattern of transmission, whereas in VWD the deficiency is related to an abnormality in von Willebrand factor (VWF), encoded by a gene located in chromosome 12. VWF carries FVIII 2 and its reduction/absence reduces FVIII plasma concentration. Type 2N is a VWD variant characterized by a defect in the FVIII binding function of VWF, 3 (with reduced FVIII but normal VWF levels. It may be misdiagnosed as hemophilia A.4 We describe a family (Figure 1) in which hemophilia A and VWD were simultaneously present: a hemophilic man (I-2) married a woman heterozygous for type 2N VWD (I-3) and their daughter (II-1) was both a carrier of hemophilia A and heterozygous for type 2N VWD. The main hemostatic findings in these subjects are reported in the Table. The proband (II-1) showed a prolonged aPTT, decreased FVIII activity (43 U/dL vs normal range 60-160 U/dL) and low FVIII/VWF:Ag ratio (0.27 vs normal > 0.8), with a normal VWF:Ag level. VWF:FVIIIB, a test which evaluates FVIII binding capacity of VWF,5 was normal when expressed as an absolute value (89.7 U/dL vs normal range 70-140 U/dL) but decreased when expressed as the ratio of VWF:FVIIIB to VWF:Ag (0.55 vs normal > 0.75). This finding suggests that FVIII binding activity was less than expected on the basis of the VWF level. The proband’s mother and half-sister (II2) had normal aPTT, FVIII, FVIII/VWF:Ag ratio and VWF:FVIIIB, but a decreased VWF:FVIIIB ratio (0.56 and 0.61, respectively). The proband’s hemophilic uncle had decreased FVIII levels but normal FVIII binding capacity of VWF (Table 1). DNA sequencing of exon 20 gene revealed that the proband, her mother, and sister had a single point mutation G2811A (nucleotide numbering including untranslated exon 1) on one allele. This substitution introduces the most frequent type 2N mutation, Arg91Gln, in the mature VWF protein. 6
The lupus anticoagulant (LAC) and anticardiolipin antibody (ACA) syndromes require particular the... more The lupus anticoagulant (LAC) and anticardiolipin antibody (ACA) syndromes require particular therapeutic approaches: thrombotic accidents are an indication for oral anticoagulant therapy (OAT), whereas severe thrombocytopenia may require the special treatments used for immunologic thrombocytopenic purpura (ITP). We describe the case of a 21-year-old male who presented with axillary vein thrombosis associated with LAC and ACA at high titers in December 1990. OAT was begun and, due to repeated episodes of thrombocytopenia, high-dose steroid therapy was later added with success. The daily steroid dose was reduced because of patent hypercortisolism, but the platelet count fell to 4 x 10(9)/L. A bone marrow biopsy was characteristic for ITP. Splenectomy was performed in June 1993, and the platelet count rapidly normalized. Platelet antibodies were always detectable before and after splenectomy. The patient is currently asymptomatic, with platelet counts above 300 x 10(9)/L at one and a ...
We read with great interest the article by Koizumi and Hatanaka1 describing the occurrence of ret... more We read with great interest the article by Koizumi and Hatanaka1 describing the occurrence of retinal vascular infarction after a photodynamic therapy (PDT) with verteporfin performed in accordance with the standard protocol. 2 The authors affirm that, “it was impossible to identify the reason for the retinal vaso-occlusive event”1 but this conclusion appears to be based on inadequate literature search and incomplete clinical assessment.3,4 In fact, various aspects of the blood testing scheduled in this patient need clarification. Specific hematologic and genetic examinations are recommended to exclude the presence of a risk correlation between individual thrombophilia and post-PDT vaso-occlusive adverse events. Particularly, in addition to a complete coagulative examination (including prothrombin time, activated partial thromboplastin time, lupus anticoagulant, fibrinogen, antithrombin, homocysteine, protein S and protein C plasmatic levels), the following gene-environment changes in hemostasis should be verified: (1) alterations of a comprehensive thrombocoagulative test (ie, ProC Global assay); (2) increase of plasma homocysteine after methionine load test; and (3) presence of several prothrombotic gene mutations (such as the hyperhomocysteinemic polymorphisms). The nonselective photothrombosis of both polypoidal and normal retinochoroidal vessels reported by Koizumi and Hatanaka1 in the PDT-irradiated area seems to be similar to the complication in our patient treated with PDT for a subfoveal choroidal neovascularization.4 Because the potential causes of abnormal occlusive response to PDT are also retrospectively investigable, we request a reply that includes a more ample assessment of the possible triggers and/or backgrounds that contribute to the occurrence of this severe adverse event
Background: Development and worldwide availability of safe and effective vaccines against severe ... more Background: Development and worldwide availability of safe and effective vaccines against severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) to fight severe symptoms of coronavirus disease 2019 (COVID-19) and block the pandemic have been a great achievement and stimulated researchers on understanding the efficacy and duration of different vaccine types.Methods: We investigated the levels of anti-SARS-CoV-2 antibodies (IgG) and neutralizing antibodies (NAbs) in 195 healthy adult subjects belonging to the staff of the University-Hospital of Ferrara (Italy) starting from 15 days up to 190 days (about 6 months) after the second dose of the BNT162b2 (Pfizer–BioNTech) mRNA-based vaccine (n = 128) or ChAdOx1 (AstraZeneca) adenovirus-based vaccine (n = 67) using a combined approach of serological and genomics investigations.Results: A strong correlation between IgG and NAb levels was detected during the 190 days of follow-up (r2 = 0.807; p < 0.0001) and was confirmed during the...
SARS-CoV-2 infection affects different organs and tissues, including the upper and lower airways,... more SARS-CoV-2 infection affects different organs and tissues, including the upper and lower airways, the lung, the gut, the olfactory system and the eye, which may represent one of the gates to the central nervous system. Key transcriptional factors, such as p53 and NF-kB and their reciprocal balance, are altered upon SARS-CoV-2 infection, as well as other key molecules such as the virus host cell entry mediator ACE2, member of the RAS-pathway. These changes are thought to play a central role in the impaired immune response, as well as in the massive cytokine release, the so-called cytokine storm that represents a hallmark of the most severe form of SARS-CoV-2 infection. Host genetics susceptibility is an additional key side to consider in a complex disease as COVID-19 characterized by such a wide range of clinical phenotypes. In this review, we underline some molecular mechanisms by which SARS-CoV-2 modulates p53 and NF-kB expression and activity in order to maximize viral replication...
The importance of host genetics and demography in coronavirus disease 2019 (COVID-19) is a crucia... more The importance of host genetics and demography in coronavirus disease 2019 (COVID-19) is a crucial aspect of infection, prognosis and associated case fatality rate. Individual genetic landscapes can contribute to understand Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) burden and can give information on how to fight virus spreading and the associated severe acute respiratory distress syndrome (ARDS). The spread and pathogenicity of the virus have become pandemic on specific geographic areas and ethnicities. Interestingly, SARS-CoV-2 firstly emerged in East Asia and next in Europe, where it has caused higher morbidity and mortality. This is a peculiar feature of SARS-CoV-2, different from past global viral infections (i.e., SARS-1 or MERS); it shares with the previous pandemics strong age- and sex-dependent gaps in the disease outcome. The observation that the severest COVID-19 patients are more likely to have a history of hypertension, diabetes and/or cardiovascular d...
In the last two decades, new insights have been gained regarding sex/gender-related differences i... more In the last two decades, new insights have been gained regarding sex/gender-related differences in cardiovascular disease (CVD). CVD represents the leading cause of death worldwide in both men and women, accounting for at least one-third of all deaths in women and half of deaths in women over 50 years in developing countries. Important sex-related differences in prevalence, presentation, management, and outcomes of different CVDs have been recently discovered, demonstrating sex/gender-specific pathophysiologic features in the presentation and prognosis of CVD in men and women. A large amount of evidence has highlighted the role of sex hormones in protecting women from CVDs, providing an advantage over men that is lost when women reach the menopause stage. This hormonal-dependent shift of sex-related CVD risk consequently affects the overall CVD epidemiology, particularly in light of the increasing trend of population aging. The benefits of physical activity have been recognized for ...
Despite convincing experimental evidence, epidemiological studies on the effects of serum uric ac... more Despite convincing experimental evidence, epidemiological studies on the effects of serum uric acid (SUA) on bone health are still conflicting since factors influencing SUA bioavailability have not been adequately considered. To shed some light on this issue, we investigated the impact of adiposity and menopause status on the relationship between SUA and bone health. We examined SUA in relation to bone mineral density (BMD) at different skeletal sites and with markers of bone metabolism in 124 pre-menopausal and 234 post-menopausal women and assessed whether adiposity, evaluated by anthropometry and dual x-ray absorptiometry (DXA), might have a discriminant role. After conservative adjustment (covariates: age, hormones treatment, smoking and time since menopause), SUA showed a significant and positive association with total hip BMD (β = 0.220, p < 0.01) among postmenopausal women, maintained also after adjustment for legs adiposity. Notably, stratification for waist circumference...
Abdominal adhesions (AA) account for the most common complication of peritoneal surgery with bowe... more Abdominal adhesions (AA) account for the most common complication of peritoneal surgery with bowel obstruction being the severest problem in the absence of effective predicting biomarkers. Anti-AA-barriers or adhesiolysis did not completely prevent bowel obstruction, although there is evidence they might reduce related complications requiring reoperation. In addition, gender-related predispositions have not been adequately investigated. We explored the role of coagulation Factor XIII (F13A1 and F13B subunit-genes) in patients following laparotomy, mostly median/lower median incision line. Globally, 426 patients (54%,♀), were PCR-SNP-genotyped for FXIIIA V34L (rs5985), FXIIIA P564L (rs5982), FXIIIA Y204F (rs3024477) and FXIIIB H95R (rs6003). Patients’ clinical phenotypes were: Group-A (n = 212), those who developed AA, and 55.2% of them developed bowel obstruction (subgroup-A1), the remaining were subgroup-A2; Group B (n = 214) were those who did not develop AA (subgroup-B1; 53.3%) o...
The effect of redox metals such as iron and copper on multiple sclerosis and amyotrophic lateral ... more The effect of redox metals such as iron and copper on multiple sclerosis and amyotrophic lateral sclerosis has been intensively studied. However, the origin of these disorders remains uncertain. This review article critically describes the physiology of redox metals that produce oxidative stress, which in turn leads to cascades of immunomodulatory alteration of neurons in multiple sclerosis and amyotrophic lateral sclerosis. Iron and copper overload has been well established in motor neurons of these diseases' lesions. On the other hand, the role of other metals like cadmium participating indirectly in the redox cascade of neurobiological mechanism is less studied. In the second part of this review, we focus on this less conspicuous correlation between cadmium as an inactive-redox metal and multiple sclerosis and amyotrophic lateral sclerosis, providing novel treatment modalities and approaches as future prospects.
Warfarin oral anticoagulant therapy (OAT) requires regular and frequent drug adjustment monitored... more Warfarin oral anticoagulant therapy (OAT) requires regular and frequent drug adjustment monitored by INR. Interindividual variability, drug and diet interferences, and genetics (VKORC1 and CYP2C9) make the maintenance/reaching of stable INR a not so easy task. HPLC assessment of warfarin/enantiomers was suggested as a valid monitoring-tool along with INR, but definite results are still lacking. We evaluated possible correlations between INR, warfarin/3'-hydroxywarfarin, and drug weekly dosage aimed at searching novel alternatives to OAT monitoring. VKORC1/CYP2C9 pharmacogenetics investigation was performed to account for the known influence on warfarin homeostasis. 133 OAT patients were recruited and assessed for warfarin/3'-hydroxywarfarin serum levels (HPLC), INR, and VKORC1 and CYP2C9 genotypes. A subgroup of 52 patients were monitored in detail (5 consecutive controls; c0-c4) till the target INR was reached. Correlation analyses were performed in both groups. In the whol...
SummaryAfter acute myocardial infarction (MI) the damaged heart has to be repaired. Factor XIII (... more SummaryAfter acute myocardial infarction (MI) the damaged heart has to be repaired. Factor XIII (FXIII) is considered a key molecule in promoting heart healing. FXIII deficiency was associated to cardiac rupture and anomalous remodelling in MI. During MI, FXIII contributes firstly to the intracoronary thrombus formation and shortly after to heal the myocardial lesion. To quantify the real contribution of FXIII in this process, and to explore its possible prognostic role, we monitored the FXIII-A subunit levels in 350 acute MI patients during the first six days (d0-d5) plus a control at 30–60 days (d30). A one-year follow-up was performed for all the patients. A transient drop in the FXIII-A mean level was noted in the whole cohort of patients (FXIII-Ad0 99.48 ± 30.5 vs FXIII-Ad5 76.51 ± 27.02; p< 0.0001). Interestingly, those who developed post-MI heart failure showed the highest drop (FXIII-Ad5 52.1 ± 25.2) and they already presented with low levels at recruitment. Similarly, th...
Annales françaises d'Oto-rhino-laryngologie et de Pathologie Cervico-faciale, 2012
This study is the first recognition of genetic implications (i.e. SNPs) in the field of sudden se... more This study is the first recognition of genetic implications (i.e. SNPs) in the field of sudden sensorineural hearing loss. In detail, SNPs of iron homeostasis genes seem to have a role in sudden sensorineural hearing loss establishment. Pharmacogenetics aspects have been discussed
1having factor VIII (FVIII) deficiency in common, albeit of different origin. In hemophilia A, th... more 1having factor VIII (FVIII) deficiency in common, albeit of different origin. In hemophilia A, the FVIII defect is associated with abnormalities in the FVIII gene, with an X-linked pattern of transmission, whereas in VWD the deficiency is related to an abnormality in von Willebrand factor (VWF), encoded by a gene located in chromosome 12. VWF carries FVIII 2 and its reduction/absence reduces FVIII plasma concentration. Type 2N is a VWD variant characterized by a defect in the FVIII binding function of VWF, 3 (with reduced FVIII but normal VWF levels. It may be misdiagnosed as hemophilia A.4 We describe a family (Figure 1) in which hemophilia A and VWD were simultaneously present: a hemophilic man (I-2) married a woman heterozygous for type 2N VWD (I-3) and their daughter (II-1) was both a carrier of hemophilia A and heterozygous for type 2N VWD. The main hemostatic findings in these subjects are reported in the Table. The proband (II-1) showed a prolonged aPTT, decreased FVIII activity (43 U/dL vs normal range 60-160 U/dL) and low FVIII/VWF:Ag ratio (0.27 vs normal > 0.8), with a normal VWF:Ag level. VWF:FVIIIB, a test which evaluates FVIII binding capacity of VWF,5 was normal when expressed as an absolute value (89.7 U/dL vs normal range 70-140 U/dL) but decreased when expressed as the ratio of VWF:FVIIIB to VWF:Ag (0.55 vs normal > 0.75). This finding suggests that FVIII binding activity was less than expected on the basis of the VWF level. The proband’s mother and half-sister (II2) had normal aPTT, FVIII, FVIII/VWF:Ag ratio and VWF:FVIIIB, but a decreased VWF:FVIIIB ratio (0.56 and 0.61, respectively). The proband’s hemophilic uncle had decreased FVIII levels but normal FVIII binding capacity of VWF (Table 1). DNA sequencing of exon 20 gene revealed that the proband, her mother, and sister had a single point mutation G2811A (nucleotide numbering including untranslated exon 1) on one allele. This substitution introduces the most frequent type 2N mutation, Arg91Gln, in the mature VWF protein. 6
The lupus anticoagulant (LAC) and anticardiolipin antibody (ACA) syndromes require particular the... more The lupus anticoagulant (LAC) and anticardiolipin antibody (ACA) syndromes require particular therapeutic approaches: thrombotic accidents are an indication for oral anticoagulant therapy (OAT), whereas severe thrombocytopenia may require the special treatments used for immunologic thrombocytopenic purpura (ITP). We describe the case of a 21-year-old male who presented with axillary vein thrombosis associated with LAC and ACA at high titers in December 1990. OAT was begun and, due to repeated episodes of thrombocytopenia, high-dose steroid therapy was later added with success. The daily steroid dose was reduced because of patent hypercortisolism, but the platelet count fell to 4 x 10(9)/L. A bone marrow biopsy was characteristic for ITP. Splenectomy was performed in June 1993, and the platelet count rapidly normalized. Platelet antibodies were always detectable before and after splenectomy. The patient is currently asymptomatic, with platelet counts above 300 x 10(9)/L at one and a ...
We read with great interest the article by Koizumi and Hatanaka1 describing the occurrence of ret... more We read with great interest the article by Koizumi and Hatanaka1 describing the occurrence of retinal vascular infarction after a photodynamic therapy (PDT) with verteporfin performed in accordance with the standard protocol. 2 The authors affirm that, “it was impossible to identify the reason for the retinal vaso-occlusive event”1 but this conclusion appears to be based on inadequate literature search and incomplete clinical assessment.3,4 In fact, various aspects of the blood testing scheduled in this patient need clarification. Specific hematologic and genetic examinations are recommended to exclude the presence of a risk correlation between individual thrombophilia and post-PDT vaso-occlusive adverse events. Particularly, in addition to a complete coagulative examination (including prothrombin time, activated partial thromboplastin time, lupus anticoagulant, fibrinogen, antithrombin, homocysteine, protein S and protein C plasmatic levels), the following gene-environment changes in hemostasis should be verified: (1) alterations of a comprehensive thrombocoagulative test (ie, ProC Global assay); (2) increase of plasma homocysteine after methionine load test; and (3) presence of several prothrombotic gene mutations (such as the hyperhomocysteinemic polymorphisms). The nonselective photothrombosis of both polypoidal and normal retinochoroidal vessels reported by Koizumi and Hatanaka1 in the PDT-irradiated area seems to be similar to the complication in our patient treated with PDT for a subfoveal choroidal neovascularization.4 Because the potential causes of abnormal occlusive response to PDT are also retrospectively investigable, we request a reply that includes a more ample assessment of the possible triggers and/or backgrounds that contribute to the occurrence of this severe adverse event
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