Intracranial Hemorrhage: A Devastating Outcome of Congenital Bleeding Disorders-Prevalence, Diagnosis, and Management, with a Special Focus on Congenital Factor XIII Deficiency.

Intracranial hemorrhage (ICH) is a medical emergency. In congenital bleeding disorders, ICH is a devastating presentation accompanied with a high rate of morbidity and mortality. The prevalence of ICH is highly variable among congenital bleeding disorders, with the highest incidence observed in factor (F) XIII deficiency (FXIIID) (∼30%). This life-threatening presentation is less common in afibrinogenemia, FVIII, FIX, FVII, and FX deficiencies, and is rare in severe FV and FII deficiencies, type 3 von Willebrand disease and inherited platelet function disorders (IPFDs). In FXIIID, this diathesis most often occurs after trauma in children, whereas spontaneous ICH is more frequent in adults. About 15% of patients with FXIIID and ICH die; the bleeding causes 80% of deaths in this coagulopathy. Although in FXIIID, the bleed most commonly is intraparenchymal (> 90%), epidural, subdural, and subarachnoid hemorrhages also have been reported, albeit rarely. As this life-threatening bleeding causes neurological complications, early diagnosis can prevent further expansion of the hematoma and secondary damage. Neuroimaging plays a crucial role in the diagnosis of ICH, but signs and symptoms in patients with severe FXIIID should trigger replacement therapy even before establishment of the diagnosis. Although a high dose of FXIII concentrate can reduce the rate of morbidity and mortality of ICH in FXIIID, it may occasionally trigger inhibitor development, thus complicating ICH management and future prophylaxis. Nevertheless, replacement therapy is the mainstay of treatment for ICH in FXIIID. Neurosurgery is performed in patients with FXIIID and epidural hematoma and a hemorrhage diameter exceeding 2 cm or a volume of ICH is more than 30 cm3. Contact sports are not recommended in people with FXIIID as they can elicit ICH. However, a considerable number of safe sports and activities have been suggested to have more benefits than dangers for patients with congenital bleeding disorders, and are hence suitable for these patients.

Diagnosis, clinical manifestations and management of rare bleeding disorders in Iran.

BACKGROUND: Rare bleeding disorders (RBDs) are heterogeneous disorders, mostly inherited in an autosomal recessive pattern. Iran is a Mideast country with a high rate of consanguinity that has a high rate of RBDs. OBJECTIVE: In this study, we present prevalence and clinical presentation as well as management and genetic defects of Iranian patients with RBDs. METHODS: For this study, all relevant publications were searched in Medlin until 2015. RESULTS AND DISCUSSION: Iran has the highest global incidence of factor XIII deficiency. Factor VII deficiency also is common in Iran, while factor II deficiency, with a prevalence of 1 per ∼3 million, is the rarest form of RBDs. Factor activity is available for all RBDs except for factor XIII deficiency, in which clot solubility remains as a diagnostic test. Molecular analysis of Iranian patients with RBDs revealed a few recurrent, common mutations only in patients with factor XIII deficiency, and considerable novel mutations in other RBDs. Clinical manifestations of these patients are variable and patients with factor XIII, factor X and factor VII more commonly presented severe life-threatening bleeding, while patients with combined factor V and factor VIII presented a milder phenotype. Plasma-derived products are the most common therapeutic choice in Iran, used prophylactically or on-demand for the management of these patients. CONCLUSION: Since Iran has a high rate of RBDs with life-threatening bleeding, molecular studies can be used for carrier detection and, therefore, prevention of the further expansion of these disorders and their fatal consequence.

Biochemical effects of oleuropein in gentamicin-induced nephrotoxicity in rats.

BACKGROUND: Oleuropein is a natural antioxidant and scavenging free radicals. In the present study, we examined effect of oleuropein on the paraoxonase 1 (PON1) activity, lipid peroxidation, lipid profile, atherogenic indexes, and relationship of PON1 activity by high-density lipoprotein-cholesterol (HDL-C) and atherogenic indices in gentamicin (GM)-induced nephrotoxicity in rats. METHODS: This is a lab trial study in Khorramabad, Lorestan province of Iran (2013). 30 Sprague-Dawley rats were divided into three groups to receive saline; GM, 100 mg/kg/day; and GM plus oleuropein by 15 mg/kg intraperitoneal daily, respectively. After 12 days, animals were anesthetized, blood samples were also collected before killing to measure the levels of triglyceride (TG), total cholesterol (TC), low-density lipoprotein (LDL), and very LDL (VLDL), HDL-C, atherogenic index, lipid peroxidation, and the activities of PON1 of all groups were analyzed. Data were analyzed, and P < 0.050 was considered significant. RESULTS: Oleuropein significantly decreased lipid peroxidation, TG, TC, LDL, VLDL, atherogenic index, atherogenic coefficient (AC), and cardiac risk ratio (CRR). HDL-C level was significantly increased when treated with oleuropein. The activity of PON1 in treated animals was (62.64 ± 8.68) that it was significantly higher than untreated animals (47.06 ± 4.10) (P = 0.047). The activity of PON1 in the untreated nephrotoxic rats was significantly lower than that of control animals (77.84 ± 9.43) (P = 0.030). Furthermore, the activity of PON1 correlated positively with HDL-C and negatively with AC, CRR 1, and CRR 2 in the treated group with oleuropein. CONCLUSION: This study showed that oleuropein improves PON1 activity, lipid profile, and atherogenic index and can probably decrease the risk of cardiovascular death in nephrotoxic patients.