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Marchiafava Micheli syndrome [keywords]
- [Case report; Two cases of paroxysmal nocturnal hemoglobinuria with preceding cytopenia]. [Journal Article]
- Nihon Naika Gakkai Zasshi 2014 Jun 10; 103(6):1385-7.
- Paroxysmal nocturnal hemoglobinuria presenting as cerebral venous sinus thrombosis: a case report. [Journal Article]
- Int Arch Med 2014.:39.
Paroxysmal Nocturnal Hemoglobinuria (PNH) is a rare type of acquired hemolytic anemia that is frequently associated with thrombophilia. It may rarely present with cerebral venous sinus thrombosis, which manifests clinically with signs of raised intracranial pressure and requires lifelong anticoagulation therapy. One such rare presentation was seen in a 28 years old male who had history of recurrent episodes of passing red colored urine and this time presented with severe headache. He was diagnosed to have cerebral venous sinus thrombosis and on further workup was found to be suffering from PNH.
- Paroxysmal nocturnal hemoglobinuria in an 86 year old woman. [JOURNAL ARTICLE]
- Rev Clin Esp 2014 Aug 12.
- Delayed duodenal obstruction after intramural hematoma in a patient with paroxysmal nocturnal hemoglobinuria: A case report. [JOURNAL ARTICLE]
- Int J Surg Case Rep 2014 Jul 24; 5(9):605-607.
Paroxysmal nocturnal hemoglobinuria (PNH) is a clonal stem cell disorder of hematopoietic cells. Gastrointestinal complications of PNH are rare and mostly related with intravascular thrombosis or intramural hematoma.We describe a case of a man with PNH complicated by intramural duodenal hematoma initially treated with supportive care. Three months after his first admission; he was admitted to the emergency department with abdominal pain, nausea and vomiting. He had undergone to surgery because of duodenal obstruction was treated with duodenojejunal by-pass surgery.Patients were healed from gastrointestinal complications could suffer from gastrointestinal strictures, which cause wide spread symptoms ranging from chronic abdominal pain and anorexia to intestinal obstruction.We report a rare intestinal obstruction case caused by stricture at the level of ligamentum Treitz with PNH. The possibility simply has to be borne in mind that strictures can be occurring at hematoma, ischemia or inflammation site of gastrointestinal tract.
- A novel CRIg-targeted complement inhibitor protects cells from complement damage. [JOURNAL ARTICLE]
- FASEB J 2014 Aug 11.
The inappropriate activation of complement may contribute to various immune diseases. The alternative pathway (AP) predominates during complement activation regardless of the initiating pathways. Hence, the main AP regulator factor H (FH) holds great potential as an attractive therapeutic intervention. In addition, complement receptor of the immunoglobulin superfamily (CRIg) has been demonstrated to inhibit AP and, more notably, still specifically binds to C3b/iC3b. We thus developed novel CRIg-targeted complement inhibitors by connecting the functional domains of CRIg and FH, which we termed CRIg-FH and CRIg-L-FH. CRIg-L-FH, slightly more potent than CRIg-FH, considerably inhibited both AP- and also classical pathway (CP)-mediated hemolysis and successfully eliminated the deposition of C3b/iC3b. Kinetic analysis further revealed that the binding affinity constant (KD) of CRIg/FH was in the micromolar range, consistent with its long-lasting binding to complement-attacked cells. CRIg-L-FH efficiently protected aberrant erythrocytes of patients with paroxysmal nocturnal hemoglobinuria (PNH) from AP- and CP-mediated complement damage (IC50 was 22.43 and 64.69 nM, respectively). Moreover, CRIg-L-FH was found to inhibit complement activation induced by the anti-Thy1 antibody in a mesangioproliferative glomerulonephritis (MPGN) rat model. Hence, CRIg-L-FH protects glomerular mesangial cells (GMCs) from complement-mediated injury and proliferative lesions. These findings strongly suggest that CRIg/FH is a potential therapeutic drug candidate for a range of complement-mediated diseases.-Qiao, Q., Teng, X., Wang, N., Lu, R., Guo, L., Zhang, X., Du, Y., Wang, W., Chen, S., Wu, Q., He, G., Wang, Y., and Hu, W. A novel CRIg-targeted complement inhibitor protects cells from complement damage.
- Humanized cobra venom factor: Structure, activity, and therapeutic efficacy in preclinical disease models. [JOURNAL ARTICLE]
- Mol Immunol 2014 Jul 22.
The complement system is an integral component of both innate and adaptive immunity. However, complement is also a pathogenetic factor in many diseases. The development of agents for therapeutic complement inhibition is the topic of intense investigations by many investigators. We have developed a distinctly different therapeutic approach: complement depletion rather than inhibition. This approach is based on cobra venom factor (CVF), a C3 analog known to be able to safely deplete complement. This manuscript will briefly review the structure and activity of CVF, along with its similarities and differences to C3. Exploiting the knowledge of the structure/function relationship of CVF and C3, we created derivatives of human C3 which display the CVF-like activity of depleting complement, referred to as humanized CVF (hCVF). This review describes the structure and activity of hCVF, including the important property of not cleaving C5. The efficacy of hCVF for therapeutic complement depletion in nine preclinical models diseases with complement pathology is reviewed, including reperfusion injury, age-related macular degeneration (AMD), paroxysmal nocturnal hemoglobinuria (PNH), and immunogenicity of Factor VIII in hemophilia A. Complement depletion is characterized by the absence of toxicity, even after intra-arterial injection into the pulmonary artery of primates. No immunogenicity has been observed.
- [Abnormal WT1 gene expression in paroxysmal nocturnal hemoglobinuria]. [English Abstract, Journal Article]
- Zhonghua Xue Ye Xue Za Zhi 2014 Jul 14; 35(7):596-600.
To explore the pathogenesis of abnormal WT1 expression in paroxysmal nocturnal hemoglobinuria (PNH).The expression of WT1 mRNA in CD59⁻ and CD59⁺ bone marrow mononuclear cells (BMMNC) were measured by semi-quantitative reverse transcription PCR. After WT1 gene silence by RNA interference (RNAi) technology, biological characteristics of BMMNC were investigated by flow cytometry.The relative expression of WT1 mRNA in PNH CD59⁻ BMMNC (1.06±0.12) was significantly higher than that in PNH CD59⁺ BMMNC (0.90±0.12) and normal BMMNC (0.86±0.05, P<0.05), but there was no significant difference between PNH CD59⁺ BMMNC and normal BMMNC (P>0.05). WT1 mRNA expression in PNH was positively correlated with the proportion of CD59⁻ cells (r²=0.490, P=0.016), but had no relationship with the proportion of CD59⁺ cells. After WT1 gene silence by siRNA in PNH CD59⁻ BMMNC, WT1 mRNA expression was decreased. The proportions of G0/G1 phase in PNH CD59⁻ cell blank control group and siRNA-scr transfected group were (92.73±3.71)% and (93.06±4.14)%, and the proportions of S phase were (6.99±3.61)% and (6.73±4.08)%, respectively. The proportions of G0/G1 and S phase in siRNA-WT1 transfected group was (94.46±3.71)% and (5.40±3.55)%, respectively. There were significant differences in the proportions of G0/G1 phase and S phase among the controls, siRNA-WT1 transfected group and siRNA-scr transfected group (P<0.05). The rate of apoptosis in siRNA-WT1 transfected group [(35.91±22.36)%] was significantly higher than those in controls [(26.12±17.10)%] and siRNA-scr transfected group [(27.39±18.99)%] (P<0.05).siRNA-WT1 could effectively suppress the WT1 gene expression of CD59⁻ clone in PNH patients, inhibit its proliferation, and promote its apoptosis. WT1 gene expression might contribute to PNH clone proliferation.
- Two case studies and a review of paroxysmal cold hemoglobinuria. [Journal Article]
- Lab Med 2014; 45(3):253-8.
Paroxysmal cold hemoglobinuria (PCH) is an acquired hemolytic anemia caused by immunoglobulin G (IgG) antibodies that sensitize red blood cells (RBCs) at cold temperatures by fixing complement to the RBCs causing intravascular hemolysis on rewarming. PCH usually appears in young children as recurrent high fevers, chills, and passage of red-brown urine. The diagnostic test for PCH is the Donath-Landsteiner test, an in vitro assay for biphasic hemolysis. Herein, we present 2 cases of PCH that occurred within 12 months of each other. We quickly diagnosed the second case and treated the patient successfully, in part due to our recognition of its characteristics based on the first case. PCH is a hemolytic anemia for which there is a specific diagnostic test; the timely recognition of this entity by physicians and laboratory staff will allow prompt, supportive therapy and will raise the odds of quick resolution of hemolysis.
- Complement Blockade with a C1 Esterase Inhibitor in Paroxysmal Nocturnal Hemoglobinuria. [JOURNAL ARTICLE]
- Exp Hematol 2014 Jul 14.
Paroxysmal nocturnal hemoglobinuria (PNH) is a rare, clonal, hematopoietic stem cell disorder that manifests with a complement-mediated hemolytic anemia, bone marrow failure and a propensity for thrombosis. These patients experience both intra- and extravascular hemolysis in the context of underlying complement activation. Currently eculizumab effectively blocks the intravascular hemolysis PNH. There remains an unmet clinical need for a complement inhibitor with activity early in the complement cascade to block complement at the classical and alternative pathways. C1 esterase inhibitor (C1INH) is an endogenous human plasma protein that has broad inhibitory activity in the complement pathway through inhibition of the classical pathway by binding C1r and C1s and inhibits the mannose-binding lectin-associated serine proteases in the lectin pathway. In this study, we show that commercially available plasma derived C1INH prevents lysis induced by the alternative complement pathway, of PNH erythrocytes in human serum. Importantly, C1INH was able to block the accumulation of C3 degradation products on CD55 deficient erythrocytes from PNH patient on eculizumab therapy. This could suggest a role for inhibition of earlier phases of the complement cascade than that currently inhibited by eculizumab for incomplete or non-responders to that therapy.
- Misleading hemoglobin a1c levels in a patient with paroxysmal nocturnal hemoglobinuria. [Journal Article]
- Am J Clin Pathol 2014 Aug; 142(2):261-5.
We report a case of a patient with diabetes mellitus and unexpectedly low hemoglobin A1c results associated with paroxysmal nocturnal hemoglobinuria (PNH). We review the impact of shortened RBC half-life on the interpretation of hemoglobin A1c levels.Patient history and laboratory test results were obtained from electronic medical records and analyzed.The patient's hemoglobin A1c declined in parallel to worsening anemia after the diagnosis of PNH. However, elevated serum glucose (random), fructosamine, and glycated albumin suggest ongoing hyperglycemia. Together, these results argue that the decline in hemoglobin A1c was due to decreased RBC survival secondary to PNH.Hemoglobin A1c levels must be interpreted with caution in patients with hematologic diseases that change RBC survival. Serum fructosamine and glycated albumin measurements are alternative measures of time-averaged blood glucose control and may be useful in this subset of patients.