Antithrombotic secondary prophylaxis with low dose of apixaban or rivaroxaban in the onco-hematologic patients: comparison with non-neoplastic patients.

Management of cancer-associated thrombosis (CAT) is usually performed employing low molecular weight heparin (LMWH) or direct oral anticoagulants (DOACs). Low-intensity DOACs are the mainstay for extended duration therapy for VTE in non-oncologic patients. The aim of our study was to evaluate the efficacy and the safety of low doses of apixaban or rivaroxaban as secondary prophylaxis in patients affected by hematological malignancies with follow-up > 12 months. We report an observational, retrospective, single-center study that evaluated consecutive patients referred to our center between January 2016 and January 2023. The DOACs were administered at full dose during the acute phase of VTE and then at low dose for the extended phase. We included 154 patients: 53 patients affected by hematological malignancies compared to 101 non-neoplastic patients. During full-dose treatment, no thrombotic recurrences were observed in the two groups. During low-dose therapy, 2 (1.9%) thrombotic events (tAE) were observed in the control group. During full-dose treatment, the rate of bleeding events (bAE) was 9/154 (5.8%): 6/53 (11%) in hematological patients and 3/101 (2.9%) in non-hematological patients (p = 0.0003). During low-dose therapy, 4/154 (2.6%) bAE were observed: 3/53 (5.5%) in the hematologic group and 1 (1%) in the control group (p = 0.07). We found encouraging data on the safety and efficacy of low doses of DOACs as secondary prophylaxis in the onco-hematologic setting; no thrombotic complications were observed, and the incidence of hemorrhagic events was low.

Venous thromboembolism prophylaxis in plastic surgery: state of the art and our approach.

OBJECTIVE: The issue of prevention of thromboembolism in plastic surgery is a rather controversial subject. The actual frequency of VTE among plastic surgery patients is probably higher than we know. Although several studies have shown that chemoprophylaxis likely increases rates of re-operative hematoma by less than one percent, surgeons are strongly resistant to adopting chemoprophylaxis due to the fear of increased bleeding and its complications. MATERIALS AND METHODS: A literature review was conducted. The 2012 ACCP guidelines suggest the use of the 2005 Caprini score as the most widely used and well-validated individualized risk-stratification tool. We propose a modified 2005 Caprini score, with specific changes pertaining to plastic surgery, in which we combine a patient risk stratification model and a procedure-driven approach explicitly indicating what procedures have to be considered at high or low risk. RESULTS: The risk of venous thromboembolism in plastic surgery cannot be disregarded. However, the plastic surgery literature still lacks high-level evidence for appropriate means of VTE prophylaxis, although an increasing amount of attention has been paid to the topic. We suggest the development of an international guideline, based on plastic surgical data, using a validated risk assessment model, which combines the surgical risk with the patient-related risk. CONCLUSIONS: Determining the proper venous thromboembolism prophylaxis is a clinical decision that should be made on a patient-to-patient basis. The algorithm presented in this article is meant to simplify this complex problem and to help expedite and clarify the decision-making process.

Malignant cerebral infarction after ChAdOx1 nCov-19 vaccination: a catastrophic variant of vaccine-induced immune thrombotic thrombocytopenia.

Vaccine-induced thrombotic thrombocytopenia with cerebral venous thrombosis is a syndrome recently described in young adults within two weeks from the first dose of the ChAdOx1 nCoV-19 vaccine. Here we report two cases of malignant middle cerebral artery (MCA) infarct and thrombocytopenia 9-10 days following ChAdOx1 nCoV-19 vaccination. The two cases arrived in our facility around the same time but from different geographical areas, potentially excluding epidemiological links; meanwhile, no abnormality was found in the respective vaccine batches. Patient 1 was a 57-year-old woman who underwent decompressive craniectomy despite two prior, successful mechanical thrombectomies. Patient 2 was a 55-year-old woman who developed a fatal bilateral malignant MCA infarct. Both patients manifested pulmonary and portal vein thrombosis and high level of antibodies to platelet factor 4-polyanion complexes. None of the patients had ever received heparin in the past before stroke onset. Our observations of rare arterial thrombosis may contribute to assessment of possible adverse effects associated with COVID-19 vaccination.

Recombinant alpha-interferon 2b in the treatment of HIV-related thrombocytopenia.

OBJECTIVE: To assess the efficacy and the mechanism of action of alpha-interferon (alpha-IFN) in the treatment of HIV-related thrombocytopenia. METHODS: Thirteen HIV-positive subjects [nine men and four women with severe thrombocytopenia (platelets, < or = 30 x 10(9)/l)] were treated with alpha-IFN 2b alone at a dose of 3 x 10(6) U three times a week for 5 weeks. Haematological parameters, platelet kinetic and bone-marrow myeloid progenitor cultures [megakaryocyte colony-forming units (CFU-MK); granulocyte macrophage CFU (CFU-GM) and erythroid burst-forming units (BFU-E)] were evaluated before and after treatment in responsive subjects. RESULTS: Seven out of 13 subjects showed a partial response (platelets, 50-149 x 10(9)/l) after alpha-IFN 2b therapy. Platelet survival as evaluated by 111In-oxine significantly increased, while platelet turnover showed a slight but not statistically significant increase after treatment. The growth of bone-marrow myeloid progenitor cells decreased after alpha-IFN 2b therapy, again without statistical significance. CONCLUSION: alpha-IFN 2b may increase the platelet count in HIV-positive subjects with severe symptomatic thrombocytopenia by prolonging platelet survival. The immunomodulatory and antiviral action of this drug may be responsible for prolonged platelet survival.

Gastrointestinal causes of refractory iron deficiency anemia in patients without gastrointestinal symptoms.

BACKGROUND: The standard evaluation of a patient with iron deficiency anemia includes a complete evaluation of the gastrointestinal tract to identify a source of bleeding. However, even after a careful examination, many patients remain without a diagnosis. Because iron deficiency anemia results from iron loss or defective absorption, we sought to determine the prevalence of potential gastrointestinal sources for iron deficiency anemia in patients without gastrointestinal symptoms. METHODS: Over a 10-month period, 668 outpatients were referred to the University Hematology Department with iron deficiency anemia, defined by a hemoglobin concentration less than 14 g/dL (less than 12 g/dL in women), mean corpuscular volume less than 80 fL, and ferritin level less than 30 microg/L. After excluding patients with obvious causes of blood loss, inadequate diet, chronic diseases, or malignancies, there were 81 eligible patients, 10 of whom refused investigation. The remaining 71 patients (51 women, median age 59 years) underwent colonoscopy, as well as gastroscopy with gastric (antrum and body) and duodenal biopsies. RESULTS: A likely cause of iron deficiency anemia was detected in 60 patients (85%). Diseases associated with bleeding were found in 26 patients (37%), including colon cancer (10 patients), gastric cancer (2), peptic ulcer (7), hiatal hernia with linear erosions (5), colonic vascular ectasia (3), colonic polyps (2), and Crohn's disease (1). Causes not associated with bleeding were found in 36 patients (51%), including 19 with atrophic gastritis, 4 with celiac disease, and 13 with Helicobacter pylori gastritis. Six (8%) patients had coincident gastrointestinal findings, and 11 (15%) had no cause identified. Patients with an identified nonbleeding-associated cause were younger than those with a bleeding-associated cause (median, 56 vs 70 years; P = 0.001) and included 59% of women (n = 30) versus 30% of men (n = 6) (P = 0.04). Hemoglobin level was not related to the site and severity of disease. CONCLUSION: Gastrointestinal diseases that do not usually cause bleeding are frequently associated with iron deficiency anemia in patients without gastrointestinal symptom or other potential causes of gastrointestinal bleeding.

Comparison between subcutaneous and intravenous DDAVP in mild and moderate hemophilia A.

Sixteen patients with mild and moderate hemophilia were given Desmopressin (DDAVP) subcutaneously in the absence of any actual bleeding. The response to the drug - in terms of factor VIII coagulant activity rise - became apparent 15 min after the injection, reaching the maximal response after one hour (means 3.2 times the baseline levels; SD 1.21). This response was not different from that elicited using the intravenous route in 18 hemophiliacs of comparable severity after the same time interval. No local or general side-effects were recorded after the subcutaneous administration of DDAVP. We therefore conclude that the subcutaneous route adds further evidence to the reliability of this alternative treatment in mild factor VIII deficiencies, thus making home treatment with this vasopressin analogue possible.

Antibody to hepatitis C virus after a vapour-heated factor VIII concentrate. The Study Group of the Fondazione dell'Emofilia.

To evaluate whether or not clotting factor concentrates exposed to virucidal procedures transmitted hepatitis C, sera obtained in 1984-1986 from 27 previously untreated hemophiliacs infused with a vapour-heated factor VIII concentrate were tested retrospectively for the antibody to the hepatitis C virus (anti-HCV). A 2-year-old hemophiliac, negative for anti-HCV before administration of concentrate, seroconverted at week 12 and remained anti-HCV positive thereafter. Both his parents were anti-HCV negative and he had no other household contact. The patient had also become HBsAg positive at week 8 and had at the same time a marked elevation of alanine aminotransferase. His double infection with the hepatitis B and C viruses indicates that hot vapour was not completely effective in inactivating these viruses.

Autoimmune thrombocytopenic purpura in pregnancy: maternal risk factors predictive of neonatal thrombocytopenia.

Pregnancy in ATP women is not unusual. The problem of this association concerns the possibility of disease transmission to the fetus due to the crossing of maternal antiplatelet antibodies through the placenta. Maternal risk factors predictive of neonatal thrombocytopenia, can be identified as follows: severe thrombocytopenia, previous splenectomy, high titre of PA-IgG and/or SPB-IgG. In 63 pregnancies in ATP patients, we have evaluated whether the above maternal risk factors, considered in the third trimester, can provide useful criteria for the prediction of neonatal thrombocytopenia. In the third trimester, the distribution of maternal risk factors was as follows: 0 in 7 cases, 1 in 27 cases, 2 in 15 cases, 3 in 12 cases, 4 in 2 cases. From a statistical evaluation, the neonatal platelet values and the maternal risk factors seem inversely correlated (r -0.437; p = 0.0005). In particular, neonatal and maternal platelet count correlated positively (r = 0.249; p = 0.025); moreover, neonatal platelet count correlated negatively with Splenectomy (r = -0.209; p = 0.05), PA-IgG (r = -0.401; p < 0.0005) and SPB-IgG (r = -0.338; p < 0.005). We tried to apply a multiple regression model for all the above parameters which appears statistically significant (p = 0.001); the variability was about 30%. This regression model could be validated if applied to a larger number of cases, and it could represent an alternative to the invasive methods used for the diagnosis of neonatal thrombocytopenia.

Clinical evaluation of subcutaneously administered DDAVP.

1-deamino-8D-arginine vasopressin was given subcutaneously at the dosage of 0.3 micrograms/Kg. b.w. to 24 mild factor VIII deficient patients (16 mild, 2 moderate hemophiliacs and 6 patients with von Willebrand's Disease), to treat bleedings (10 episodes) or to prevent bleeding during and after dental extractions (6 extractions) and surgery (11 interventions). None of the patients who underwent surgery bled. The vasopressin analogue was effective in the early treatment of muscle hematomas and promptly stopped all mucosal hemorrhages. Most of the patients treated for "spontaneous" bleedings performed self-injections at home. The drug was administered in two pharmaceutical forms (4 and 40 micrograms/ml): no differences in the clinical outcome were found. No significant side effects were recorded. The subcutaneous route of DDAVP administration thus seems to be particularly useful (mainly in the concentrated pharmaceutical form) in treating mild factor VIII deficiencies even on self- and home-treatment basis.

Endoscopic Evaluation of the Upper Gastrointestinal Tract is Worthwhile in Premenopausal Women with Iron-Deficiency Anaemia Irrespective of Menstrual Flow.

BACKGROUND: In premenopausal women, iron-deficiency anaemia is common and menstrual flow is often held responsible, but it is not clear whether these women should be submitted to gastrointestinal (GI) evaluation. We aim to prospectively investigate whether premenopausal women with iron-deficiency anaemia benefit from GI evaluation regardless of menstrual flow. METHODS: The study population comprised 59 consecutive premenopausal women with iron-deficiency anaemia. Excluded were women with obvious or suspected causes of anaemia and those ≤21 years. Heavy menstrual loss was not considered an exclusion criterion. All subjects had: complete blood count, ferritin, non-invasive testing by faecal occult blood (FOB), 13C-urea breath test (13C-UBT), anti-tissue transglutaminase antibodies (tTG) and gastrin levels. Gastroscopy with antral (n = 3), corporal (n = 3) and duodenal (n = 2) biopsies was performed in women with positive 13C-UBT or tTG titre or hypergastrinaemia. RESULTS: Heavy menstrual loss was present in 50.8%. Non-invasive tests were positive in 40/59 (67.8%): 30 had positive 13C-UBT, 12 had hypergastrinaemia, 7 had positive tTG and 3 had positive FOB. Women tested positive were similar to those tested negative as far as concerned age, haemoglobin and ferritin levels and heavy menstrual flow (55% versus 42.1%). All 40 women tested positive underwent gastroscopy with biopsies. Four (10%) had bleeding-associated lesions and 34 (85%) had non-bleeding-associated lesions. As regards upper GI findings, no differences were observed between women with normal and those with heavy menstrual flow. No lower GI tract lesions were detected in the three women with positive FOB. CONCLUSIONS: Our data suggest that premenopausal women with iron-deficiency anaemia benefit from endoscopic evaluation of the upper GI tract irrespective of menstrual flow.

Antithrombin III infusion suppresses the hypercoagulable state in adult acute lymphoblastic leukaemia patients treated with a low dose of Escherichia coli L-asparaginase. A GIMEMA study.

Thrombotic events have been reported in acute lymphoblastic leukaemia patients, especially during or after L-asparaginase administration. A so-called L-asparaginase associated coagulopathy has been well recognized, being characterized by a hypercoagulable state (decrease of antithrombin III, plasminogen, protein C, protein S and increase of prothrombin fragment F1 + 2, thrombin-antithrombin complexes and fibrinopeptide A). The aim of this study was to determine whether the supplementation of antithrombin III (AT-III) concentrates could improve the L-asparaginase associated coagulopathy, thereby blocking the activation of the haemostatic system. In 25 adult patients with acute lymphoblastic leukaemia (M 19, F6, mean age 34 years) antithrombin III (AT-III) concentrates were administered at daily doses of 50 U/kg for 10 consecutive days from the beginning of L-asparaginase therapy (6,000 U/m2/day s.c. for 7 days), given according to the GIMEMA ALL 0288 trial. A marked increase of antithrombin III was recorded on days IV-VIII-XI (P < 0.001). No changes in protein C, protein S, plasminogen, alpha 2-antiplasmin, factor VII and platelet count were observed and there was no increase in markers of hypercoagulability. There was no evidence of disseminated intravascular coagulation. In conclusion, AT-III concentrate supplementation during L-asparaginase therapy, by the achievement of high levels of antithrombin III, is associated with a lack of activation of the haemostatic system and appears to overcome the complex coagulopathy associated with L-asparaginase.

Efficacy of three different antithrombotic regimens on pregnancy outcome in pregnant women affected by recurrent pregnancy loss.

INTRODUCTION: Recurrent pregnancy loss (RPL) is a common health problem affecting 1-5% of women at reproductive age. AIM OF THE STUDY: Evaluation of three different antithrombotic treatments in women with antecedent of RPL, comparing the results in negative and positive to thrombophilic screening pregnant women. MATERIALS AND METHODS: We recruited 361 women with an antecedent of two or more pregnancy losses. From this group, 167 women became pregnant and considered for the study. The evaluated pregnant women were divided as negative/positive to thrombofilic screening: (a) 80 (48%) with negative thrombophilic screening, (b) 87 (52%) positive to thrombophilic screening. Pregnant women included in the study and considered negative or positive for thrombophilic screening, were randomized into three different therapy groups: (a) group 1: Acetil salicylic acid (ASA) 100 mg daily until third month of pregnancy, (b) group 2: low molecular-weight heparin (LMWH) - enoxaparine 40 mg daily until third month of pregnancy, (c) group 3: ASA 100 mg plus LMWH 40 mg daily until third month of pregnancy. RESULTS: In 80 negative to thrombophilic screening pregnant women, the comparison of efficacy of the three treatments, shows that all three treatment regimens were significantly effective comparing live births against fetal losses. In 87 positive to thrombophilic screening pregnant women, the comparison of efficacy for the three regimens, shows that the therapy with LMWH or LMWH plus ASA are significantly protective against fetal losses with respect to ASA, which showed a high number of fetal losses (11 live births, 18 fetal losses). COMMENT: We suggest that thromboprophylaxis is indicated in women with RPL independently from positiveness to thrombophilic markers.

Arthroscopic synovectomy in the treatment of haemophilic arthropathy: preliminary results in eight patients.

Synovectomy is a procedure which is widely used in the surgical treatment of haemophilic arthropathy: the short and long-term results have in fact sufficiently shown its effectiveness in the reduction of the number of cases of haemarthrosis. This operation, however, has the disadvantage of a reduction in joint mobility which may vary from 25% to 77%, depending on the various case series reported (Post et al., 1986; Clark, 1978; McCollough et al., 1979; Montane et al., 1986). This complication moreover, is common to all synovectomy operations, even those which are performed for synovial affections of a different nature. As the advantages of arthroscopic synovectomy as compared to open surgery are commonly known, it was decided to extend the indication to haemophilic arthropathy (Wiedel, 1985; Klein et al., 1987). The purpose of this study is to evaluate the effectiveness of arthroscopic synovectomy in 8 patients with type A haemophilia affected with severe arthropathy consequent to repeated haemarthrosis and with marked hypertrophic synovial tissue.

Splenectomy outcome in a hemophilic patient with HIV-related immune thrombocytopenia.

We report the case of a young hemophilic patient with antibodies against the human immunodeficiency virus (HIV) who was affected by immune thrombocytopenic purpura (ITP). This condition did not respond to pharmacological therapy with steroids and alpha-2b-r-IFN, and the patient was splenectomized. Immune status evaluation was performed before and after surgery and during follow-up with CD4-CD8 monoclonal antibodies and cytofluorimetric analysis in order to explore possible correlations between splenectomy and the cytologic immune regulatory system. Splenectomy resulted in a resolution of ITP with consequent disappearance of the hemorrhagic diathesis related to thrombocytopenia. Moreover, at 30 months from splenectomy the patient is still in remission, his CD4 count is not decreased, and no progression to AIDS has been evidenced. These aspects are analyzed and briefly discussed.

Therapy with Anagrelide in patients affected by essential thrombocythemia: preliminary results.

BACKGROUND: Anagrelide, an imidazo-quinazolin compound first proposed as a potent inhibitor of platelet function, was subsequently recognized as a drug able to lower the platelet number both in normal subjects and in myeloproliferative syndromes with thrombocytosis. We report our experience with Anagrelide therapy in 20 patients affected by essential thrombocythemia (E.T.). PATIENTS AND METHODS: Twenty consecutive patients with E.T. entered the study from June, 89 to July, 91. Therapy schedule was as follows: 0.5 mg every 12 hours for 7 days; subsequently the daily dose was increased by 0.5 mg/day every week until a response was obtained (a decrease of the platelet count to less than 500 x 10(9)/l = complete response; to less than 600 x 10(9)/l = partial response). RESULTS: Of 19 evaluable patients, complete response (CR) was obtained in 13 (68%) and partial response (PR) in 3 (16%). For all responders, the mean time to response was 5.2 months: mean daily dose of Anagrelide 2 mg. Side effects were recorded in 8/20 patients (40%): tachycardia (n = 4), gastrointestinal distress (n = 3), perimalleolar edema (n = 1). In 6 cases therapy was discontinued definitively. DISCUSSION: Response rate to therapy with Anagrelide is similar to that with alkylating agents and alpha 2b-recombinant interferon; furthermore, Anagrelide is a drug without cytotoxic properties. The mean daily dose able to obtain a response is 2 mg, but maintenance therapy at similar doses is always necessary. In conclusion, we can say that Anagrelide is an effective drug in the treatment of patients with E.T., but its side effects must be seriously considered. A larger study may show whether it should be considered as a "first-line" drug for all patients with E.T.

Hepatitis C virus antibody in coagulopathic patients: ELISA and RIBA methods.

Hepatitis C is an important complication of therapy with coagulation factor concentrates; in fact, more than 90% of post transfusion hepatitis is caused by hepatitis C. Evaluation of HCV antibodies has been carried out mainly with the ELISA method but this test generates false positive results. Therefore, we studied ninety coagulopathic patients with the aim of determining the prevalence of hepatitis C virus (HCV) antibodies using the ELISA and RIBA methods. Our study confirms that the ELISA method presents false positivities: of 60 ELISA positive patients, only 41 were confirmed by RIBA. We found a significant correlation between HCV positivity, ALT titre and the number of concentrates used annually. In conclusion, our data suggest that the RIBA test is a useful confirmatory method in ELISA HCV-positive patients. This fact is particularly important in coagulopathic patients, in whom progression of chronic hepatitis C to cirrhosis is elevated.

Detection of drug-dependent IgG antibodies with antiplatelet activity by the antiglobulin consumption assay.

Drug-induced thrombocytopenia is a common acquired hemorrhagic disorder. In this study 32 patients with drug-induced thrombocytopenia were examined with the antiglobulin consumption assay. Platelet-associated IgG was elevated in 19 of 20 patients that were analyzed. An increase in serum platelet bindable IgG was observed in 24 subjects after the addition of various drugs (acetylsalicylic acid, noraminopyrine, antibiotics, sulfamides, digoxin, heparin and chenodeoxycholic acid). These findings are significant for the presence of drug-dependent platelet antibodies.