Siayareh Rambally

Treatment of refractory thrombotic thrombocytopenic purpura with N-Acetylcysteine: A case report

Thrombotic thrombocytopenic purpura (TTP) is a life‐threatening disease resulting in systemic microvascular thrombosis. The disease is caused by excessive platelet (PLT) adhesion to ultra‐large (UL) von Willebrand factor (VWF) multimers inadequately cleaved by the processing enzyme ADAMTS‐13. While many cases respond to plasma exchange performed with or without concurrent corticosteroids, treatment of the 10% to 20% of patients with refractory disease is difficult. Experimental studies demonstrating that N‐acetylcysteine (NAC) inhibits PLT binding to endothelial cell–secreted and anchored UL VWF multimers suggest that NAC may be useful in the treatment of TTP.

Combining T-cell immunotherapy and anti-androgen therapy for prostate cancer

Background:Prostate cancer remains a significant health problem for men in the Western world. Although treatment modalities are available, these do not confer long-term benefit and are accompanied by substantial side effects. Adoptive immunotherapy represents an attractive alternative to conventional treatments as a means to control tumor growth.Methods:To selectively target the tumor-expressed form of Muc1 we constructed a retroviral vector encoding a chimeric antigen receptor (CAR) directed against the aberrantly-expressed extracellular portion of Muc1 called the ‘variable number of tandem repeats’.Results:We now demonstrate that T cells can be genetically engineered to express a CAR targeting the tumor-associated antigen Muc1. CAR-Muc1 T cells were able to selectively kill Muc1-expressing human prostate cancer cells. However, we noted that heterogeneous expression of the Muc1 antigen on tumor cells facilitated immune escape and the outgrowth of target-antigen loss variants of the tumor. Given the importance of androgen ablation therapy in the management of metastatic prostate cancer, we therefore also tested the value of combining conventional (anti-androgen) and experimental (CAR-Muc1 T cells) approaches. We show that CAR-Muc1 T cells were not adversely impacted by anti-androgen therapy and subsequently demonstrate the feasibility of combining the approaches to produce additive anti-tumor effects in vitro.Conclusions:Adoptive transfer of CAR-Muc1 T cells alone or in combination with other luteinizing hormone-releasing hormone analogs or antagonists should be tested in human clinical trials.

Transfusion management of factor V deficiency: three case reports and review of the literature

Factor V (FV) deficiency may be inherited as an autosomal recessive disease or acquired as a result of autoantibody formation, either spontaneously or secondary to exposure to bovine thrombin or medications. Congenital FV deficiency has traditionally been treated with plasma transfusions. However, recent evidence has suggested that platelet (PLT) transfusions may be a better alternative as FV stored within PLT alpha granules has greater procoagulant potential and is released locally at sites of vascular injury. We report three cases of FV deficiency, one congenital and two acquired, and emphasize the different management approaches.

Ischemic stroke in a patient with moderate to severe inherited factor VII deficiency

Thrombosis is known to occur in patients with rare inherited bleeding disorders, usually in the presence of a thrombotic risk factor such as surgery and/or factor replacement therapy, but sometimes spontaneously. We present the case of a 72-year-old African American male diagnosed with congenital factor VII (FVII) deficiency after presenting with ischemic stroke, presumably embolic, in the setting of atherosclerotic carotid artery stenosis. The patient had an international normalized ratio (INR) of 2.0 at presentation, with FVII activity of 6% and normal Extem clotting time in rotational thromboelastometry. He was treated with aspirin (325 mg daily) and clopidogrel (75 mg daily) with no additional bleeding or thrombotic complications throughout his admission. This case provides further evidence that moderate to severe FVII deficiency does not protect against thrombosis.

Mixing Study for Evaluation of Abnormal Coagulation Testing.

An 84-year-old woman with a history of chronic kidney disease, prior stroke, and hypertension was admitted with a 2-week history of spontaneous subcutaneous ecchymoses and hematomas. She did not have any history of bleeding disorders, preceding trauma, or other precipitating factors such as recent heparin exposure, surgical procedures, underlying liver disease, or receipt of anticoagulation agents. There was no family history of hematologic disorders. Her vital signs were normal. Physical examination showed large ecchymoses on the left arm, right shoulder, left anterior chest wall, and flank. Initial laboratory results showed isolated severe anemia. Computed tomographic imaging showed a large soft-tissue hematoma in the left chest wall without evidence of internal hemorrhage. Test results for other causes of anemia were unremarkable. Laboratory values and mixing study results are shown in the Table.

Resolution of acute hepatitis B-associated aplastic anaemia with antiviral therapy

A previously healthy 44-year-old woman presented with 3 days of worsening petechial rash, epistaxis and fatigue. Admission labs revealed pancytopenia, low reticulocyte index and elevated liver enzymes. Bone marrow biopsy demonstrated a profoundly hypocellular bone marrow without dysplasia and additional testing demonstrated an acute hepatitis B infection. In the context of an acute hepatitis B infection, elevated liver enzymes and aplastic anaemia, our patient was diagnosed with severe hepatitis-associated aplastic anaemia due to an acute hepatitis B infection. She was initiated on antiviral therapy with tenofovir and briefly received immunosuppressive therapy with a robust sustained improvement in her blood counts. Acute hepatitis B-associated aplastic anaemia is an exceptionally rare presentation of aplastic anaemia. We present acute hepatitis B-associated aplastic anaemia that resolved with antiviral therapy, which to our knowledge is the second such case reported in the literature and the first using tenofovir.