We wish to highlight that on encountering a suspicious hepatic and a colonic lesion, the possibility of TB should also be kept in mind apart from the obvious possibility of metastasis of a colonic cancer especially in an endemic country like Tunisia.
4G/5G and TPA 311 bp Ins/Del variations was performed by PCR-RFLP. To assess intergroup differences in genotype frequencies, the odds ratios (OR), their 95% confidence intervals (CI) and p-values were calculated by Fisher's exact method. Results: Distributions of the FI-A, FXIII-A, PAI-1 and TPA genotypes in patients with different clinical manifestations of VTE have shown several differences. Frequency of the TPA Del/Del genotype was significantly increased in VTE patients with the signs of PE when compared to those with isolated DVT (31.5% vs. 18.8%, respectively, OR = 2.0; 95% CI: 1.1-3.6; p = 0.029). Homozygosity for the TPA Del allele was most prevalent in patients with isolated PE (38.9% vs. 18.8% in the group "DVT only'', OR = 2.7; 95% CI: 1.3-6.0; p = 0.014). In this group, the frequency of the FI-A 312 Ala/Ala variant was 2-fold increased when compared to patients with isolated DVT (22.2% vs. 11.0%, respectively, OR = 2.3; 95% CI: 0.9-5.9; p = 0.098). In patients with the signs of PE, homozygosity for the FXIII-A 34Leu variant was observed more frequently than in the "DVT only'' group (11.2% vs. 6.5%, respectively, OR = 1.8; 95% CI: 0.7-4.6; p = 0.23). At the same time, the frequency of heterozygous FXIII-A genotype was significantly increased in patients with isolated DVT when compared to "DVT+PE'' group (48.7% vs. 30.2%, respectively, OR = 2.2; 95% CI: 1.1-4.3; p = 0.024).
Background: Acquired hemophilia A (AHA) is a rare, severe and potentially life treating bleeding disorder. It is caused by the spontaneously formed autoantibodies, which are polyclonal immunoglobulins, usually IgG directed against the FVIII. While this disorder may appear at any age, the elderly are most commonly affected. It is associated with autoimmune diseases, malignancies and pregnancy, although approximately 50% of cases are idiopathic. Patients may present with overt bleeding (hemorrhages into the skin, muscles or soft tissues and mucous membranes) or anemia due to occult hemorrhage. Treatment goals for AHA are: comprise hemostasis, inhibitor eradication and treatment of associated disorders. The mortality rate is relatively high, ranging from 6% to 8% due to extensive bleeding, elderly life, side effects and toxicity of immunosuppressive agents and concomitant diseases. Aims: In this study, we wanted to evaluate the clinical characteristics, treatment efficiency and outcome of patients with AHA. Methods: The retrospective study investigated cases of AHA at the Clinic for Hematology, Clinical Centre of Vojvodina, Serbia, from March 2016 to December 2018. We evaluated 5 patients with AHA managed at our Haemophilia Centre . Results: Out of our five patients, three were males and two females, age ranging between 44 and 88 years (mean age 67.8 years). No one had a history of previous bleeding episodes. Four had mild clinical manifestations of the disease; subcutaneous hemorrhage and soft tissue bleeds localized at the extremities, while one patient presented with massive iliopsoas muscle hematoma and upper gastrointestinal bleeding. In one patient inhibitors were associated with double malignancies (CLL, lung cancer), and in another patient with paraproteinaemia. Three patients had comorbidities including coronary artery disease, arterial hypertension, COPD and diabetes mellitus type 2. Osteoarthritis was diagnosed at one patient. The youngest patient had no associated disease or underlying medical conditions and only he did not have anemia. Activated partial thromboplastin time (aPTT) was prolonged in all patients (range 29.8 -90.1 s). In every patient low level of FVIII activity has been found. It was ranging from <1.0% to 12.0% (mean 2.69%). All bleeding episodes resolved with hemostatic replacement therapy, activated prothrombin complex concentrate -APCC (FEIBAâ) (n-3), APCC plus recombinant activated factor VII -rFVIIa (NovoSevenâ) (n-2). In our review all the patients had high-titre of inhibitors (> 5 BU/mL). The mean peak was 46.8 BU/mL (range 8.3-185). To eradicate the inhibitors, all patients received systemic corticosteroids, either alone (n-2) or in combination with cyclophosphamide (n-3). In all patients, management was successful, with complete response (CR) within 2 months of treatment initiation. Only one patient, with the highest titre of inhibitors, relapsed after 2 months. All of the other patients were in remission over the 2 years of follow-up. One patient died of lung cancer complications...
Results: Serum OPG concentrations increased throughout the study period (p = 7.26x10 -5 ) while RANKL concentrations did not change (p = 0.19). The OPG:RANKL ratio exhibited a 6.2-fold increase between Days 1 and 5. CTX-1 concentrations were lower (p = 0.006) 30 minutes after the 50 U/kg FVIII infusion. CTX-1 response for each participant was assessed using linear regression throughout the time course. Spine L1-L4 Z-score (SZ) and Hip Total Z-score (HTZ) correlate with CTX-1 response (p = 3.4x10 -4 and 0.014, respectively). The mean age of participants was 25.2 ± 2.1 at time of first study visit. Participants had a mean SZ of −0.74 ± 0.34, HTZ of −0.17 ± 0.32, Hip Neck Z-score (HNZ) of −0.16 ± 0.35, and HJHS of 20 ± 5. HTZ and HNZ decreased significantly with patient age (p = 0.027 and 0.032) while SZ and HJHS did not (p = 0.18 and 0.16). Consequently, age correction was applied to BMD comparisons. Statistical comparisons between HAL, EQ-5D-3L, and BHQ answers, BMD data, and HJHS are shown in Table 1. Summary/Conclusion: This prospective study demonstrates a relationship between FVIII deficiency and bone disease in PwH. OPG acts as a decoy ligand to RANKL, inhibiting osteoclastic bone resorption. The observed increase in OPG:RANKL ratio suggests FVIII has a direct impact on this pathway. Decreased CTX-1 concentrations following factor infusion and correlations between CTX-1 response and BMD further suggests that FVIII plays a role in moderating bone remodeling. Hemophilia-associated bone and joint pathology is associated with decreased quality of life. Correlations between BMD and questionnaire responses demonstrate that poor bone and joint health is physically limiting, causes discomfort, and negatively impacts perceptions of personal well-being. Furthermore, correlations between BMD and HJHS and ISTH-BAT responses (Table 1) illustrate a relationship between bleeding management and skeletal health. PwH with lower BMD report more nose and gum bleeds, suggesting a link between FVIII replacement and skeletal health. Bleeds in the extremities were not correlated with decreased BMD or increased HJHS, but abdominal (stomach, iliopsoas) and other bleeds were. Analysis of these data is ongoing.
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