Thrombin activatable fibrinolysis inhibitor (TAFI): relationship to hemostatic alteration in patients with beta-thalassemia.

Profound hemostatic changes have been observed among thalassemic patients. Thrombin activatable fibrinolysis inhibitor (TAFI) is a newly discovered protein that potentially attenuates fibrinolysis. The authors aimed to investigate plasma level of TAFI in beta-thalassemia patients in relation to clinical severity and hemostatic alteration. Fifty-one thalassemic patients (mean age 10.79 +/- 5.59 years) (21 splenectomized thalassemia major patients, 18 nonsplenectomized thalassemia major patients, 12 nonsplenectomized thalassemia intermedia) were recruited from Pediatric Hematology Clinic, Ain Shams University; in addition, 32 healthy age- and sex-matched controls (10.31 +/- 5.58 years) were also included. In addition to clinical assessment, laboratory investigations included complete blood count (CBC), hemoglobin electrophoresis, prothrombin time (PT), activated partial thromboplastin time (PTT), liver function tests, viral hepatitis markers, serum ferritin, and plasma TAFI levels. Nine out of 51 patients (17.5%) suffered from bleeding manifestations mainly in the form of epistaxis; none of the studied patients had thromboembolism. Significant reduction in TAFI levels was shown in thalassemic patients compared to controls (P < .0001), in splenectomized compared to nonsplenectomized thalassemia group (P < .0001), and in thalassemia major compared to thalassemia intermedia group (P < .0001). Negative correlation was present between TAFI levels and both liver enzymes and serum ferritin levels (P < .05). Thalassemic patients suffering from bleeding showed lower mean TAFI levels compared to those not suffering from bleeding (P < .001). Marked reduction in TAFI levels was observed in thalassemic patients with splenectomy, altered liver functions, and poor chelation who therefore might be at a higher risk for altered hemostasis.

Rapidly deteriorating renal function with membranoproliferative glomerulonephritis Type 1 associated with hepatitis C treated successfully with steroids and antiviral therapy: a case report and review of literature.

INTRODUCTION: The hepatitis C virus (HCV) infection is associated with several renal diseases including mixed essential cryoglobulinemia, membranoproliferative glomerulonephritis (MPGN) and less frequently membranous nephropathy and crescentic glomerulonephritis. We present a case of HCV-associated cryoglobulin-negative, MPGN Type 1 with features of early crescents and rapidly deteriorating renal function requiring urgent treatment. CASE: A 35-year-old male was admitted with history of arthralgia and erythematous rash. His past medical history included being an intravenous drug abuser. Biochemistry test showed raised serum creatinine of 150 micromol/l. He had nephrotic range proteinuria of 6 g/day and a serum albumin of 23 g/l. Viral serology for hepatitis B and HIV was negative but confirmed evidence of HCV infection with genotype 3A and viral load of 151,014 copies. He had a renal biopsy and histology demonstrated features of crescentic MPGN Type 1. His renal function deteriorated rapidly with his serum creatinine rising to 300 micromol/l over 2 days. We commenced treatment with intravenous methylprednisolone, 500 mg once daily (o.d.) for 3 days, followed by oral prednisolone 40 mg o.d. Concurrently, pegylated Interferon- (IFN) I+/- was commenced. After a 2-week treatment, his renal function showed remarkable recovery with creatinine reduced to 140 micromol/l. After 3 months, ribavirin was added when his renal function remained stable. He had tolerated his treatment without any major side effects. At 6 months follow-up clinic, his renal function was normal with serum creatinine of 69 micromol/l, 24-h urinary protein had dropped to 0.35 g/day, serum albumin increased to 38 g/l and HCV PCR was negative. DISCUSSION: The current treatment strategy of HCV-associated renal diseases includes targeting viral trigger HCV with interferon and ribavirin. Both IFN-I+/- and ribavirin have their limitation and adverse effects. In a clinical scenario where there is evidence of rapidly deteriorating renal function with crescentic glomerulonephritis, cautious use of immunosuppressive therapy may well be essential in the acute stage to halt the progression of kidney damage. Literature review of the treatment strategy for MPGN Type 1, cryoglobulin-negative with early features of crescents associated with HCV showed that there was no report or guideline available. CONCLUSIONS: To our knowledge, this is the first case in the literature of rapidly progressing MPGN Type 1 associated with HCV and nephrotic syndrome treated successfully with antiviral drugs and steroids concurrently. Our case highlights an important treatment strategy and may be beneficial to nephrologists facing this clinical scenario in the future. However, a randomized controlled trial is required to evaluate the efficacy of this treatment combination before it can be a standard treatment.

COX-1 and COX-2 expression in stage I and II invasive cervical carcinoma: relationship to disease relapse and long-term survival.

COX-1 and COX-2 are members of the cyclooxygenase (COX) family, which influence tumor invasion and apoptosis. The objective of the study was to assess the relationship between COX-1 and COX-2 expression in early-stage disease and subsequent disease relapse and long-term survival. Women with FIGO stage I and II cervical carcinoma, younger than 50 years, treated between 1981 and 1990 were included. COX-1 and COX-2 expressions in the tumors were assessed by immunohistochemistry. COX-1 and COX-2 were expressed in 61% (17/28) and 57% (16/28) of tumors, respectively. COX-1 nonexpressers showed an improved overall survival compared to expressers (log-rank test, P= 0.09). There was no significant difference in the overall survival in COX-2 nonexpressers compared to expressers (P= 0.6). Out of eight women with disease relapse, COX-1 or COX-2 expression was noted in six of eight tumors, and both were expressed in five of eight tumors. Our preliminary data suggest an adverse prognosis with COX-1 expression in early-stage cervical carcinoma and a trend toward COX-1 expression in disease relapse. The association between COX-2 expression and a worse prognosis was not proven in this study.

Villoglandular adenocarcinoma of the cervix: clarity is needed on the histological definition for this difficult diagnosis.

BACKGROUND: Villoglandular adenocarcinoma (VGA) of the cervix is reported as a variant of a cervical adenocarcinoma with a good prognosis. CASES: We present two cases histologically reported as a villoglandular adenocarcinoma of the cervix that have recurred and progressed rapidly since initial treatment. External histopathological review suggested both had a prominent villoglandular pattern but with an associated underlying well-differentiated adenocarcinoma. CONCLUSION: The diagnosis of VGA is difficult. Current literature is not entirely consistent in the presented definition, and further clarity is needed. Because of the rarity of VGA and the difficulty but importance of the diagnosis, we would feel that a central review of all cases of VGA is warranted. This would assist in diagnosis and also in obtaining accurate follow-up data.