Membrane autoantibodies in systemic lupus erythematosus: a case of autoimmune hemolytic anemia, antiphospholipid antibodies, and transient acquired activated protein C resistance

BACKGROUND: Warm autoimmune hemolytic anemia and antiphospholipid antibodies (which include lupus anticoagulants and anticardiolipin [ACL] antibodies) are associated, respectively, with approximately 10 and 40 percent of cases of systemic lupus erythematosus (SLE). This study reports a case of SLE presenting with an unusual constellation of findings that included an immunoglobulin M (IgM) cold autoantibody of high thermal amplitude, high‐titer ACL antibodies, and transient acquir ed activated protein C resistance. CASE REPORT: A previously untransfused, nulligravid 17‐year‐old woman without a significant medical history presented with signs and symptoms of SLE and an extravascular hemolytic anemia. Spontaneous agglutination was noted in blood samples collected for testing. Serologic testing revealed a normal‐titer, high‐thermal‐amplitude IgM red blood cell (RBC) autoantibody but no additional RBC antibodies in the patient's plasma. Additional testing was significant for a high‐titer ACL IgM and a positive test for activated protein C resistance (a screening test for the Factor [F]V Leiden mutation), which prompted initiation of prophylactic anticoagulation. Confirmatory DNA testing for FV Leiden, however, was negative. The patient's symptoms, anemia, RBC autoagglutinins, ACL antibodies, and activated protein C resistance all resolved after 6 weeks of immunosuppression. CONCLUSION: This case illustrates the wide range of clinical and laboratory findings that autoantibodies against cellular membranes may produce. IgM autoagglutinins of high thermal amplitude associated with a significant extravascular hemolytic anemia may be a presenting feature of SLE. Concomitant antiphospholipid antibodies may interfere with partial thromboplastin time–based tests of hypercoagulability such as that for activated protein C resistance.     

Acute hemolysis of transfused A2 red cells by an auto-HI antibody

BACKGROUND: Anti-HI is a common cold autoantibody that complicates serologic testing for underlying alloantibodies and has only rarely been associated with hemolysis. An unusual case of an acute hemolytic transfusion reaction (AHTR) due to an anti-HI autoantibody in a subgroup A1 patient transfused with A2 red blood cells (RBCs) is reported. CASE REPORT: A 56-year-old man presented to the hospital with anemia and gastrointestinal tract bleeding. His medical history was significant for congestive heart failure, obesity, and pulmonary hypertension. On admission, he was noted to have a hemoglobin level of 7.7 g per dL and therefore transfusion of RBCs was ordered. The patient was group A, D- with a reactive antibody screen due to a cold autoantibody with HI specificity. Further serologic investigation did not detect any alloantibodies. The patient was issued an electronically cross-matched group A, D- unit of RBCs. Several hours after the transfusion, he was found to be producing "Coca-cola"-colored urine with gross hemoglobinemia visible in a posttransfusion specimen, indicating an AHTR. A transfusion reaction investigation excluded mistransfusion or a missed alloantibody and instead revealed that the patient's anti-HI had a high thermal amplitude and that the implicated unit of RBCs was from the A2 subgroup. The patient subsequently tolerated transfusion of a unit of group A1 RBCs through a blood warmer without any signs or symptoms of hemolysis. CONCLUSION: This case illustrates that anti-HI autoantibodies rarely may behave like alloantibodies and cause AHTRs. Subsequent RBC transfusion with an appropriate ABO group or subgroup through a blood warmer is well tolerated.     

Brain derived neurotrophic factor treatment reduces inflammation and apoptosis in experimental allergic encephalomyelitis

Multiple sclerosis is an inflammatory disease of the central nervous system (CNS) which includes a neurodegenerative component. Brain derived neurotrophic factor (BDNF) is a neuroprotective agent which might be useful in preventing neurodegeneration but its application has been limited because the blood brain barrier restricts its access to the CNS. We have developed a novel delivery system for BDNF using transformed bone marrow stem cells (BMSC) and undertook studies of EAE to determine whether the delivery of BDNF could reduce inflammation and apoptosis. Mice receiving BDNF producing BMSC had reduced clinical impairment compared to control mice receiving BMSC that did not produce BDNF. Pathological examination of brain and spinal cord showed a reduction in inflammatory infiltrating cells in treated compared to control mice. Apoptosis was reduced in brain and spinal cord based on TUNEL and cleaved Caspase-3 staining. Consistent with the known mechanism of action of BDNF on apoptosis, Bcl-2 and Akt were increased in treated mice. Further studies suggested that these increases could be mediated by inhibition of both caspase dependent and caspase independent pathways. These results suggest that the BDNF delivered by the transformed bone marrow stem cells reduced clinical severity, inflammation and apoptosis in this model.     

Utilizing a PLASMIC score-based approach in the management of suspected immune thrombotic thrombocytopenic purpura: a cost minimization analysis within the Harvard TMA Research Collaborative

The PLASMIC score is a recently described clinical scoring algorithm that rapidly assesses the probability of severe ADAMTS13 (a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13) deficiency among patients presenting with microangiopathic haemolytic anaemia. Using a large multi-institutional cohort, we explored whether an approach utilizing the PLASMIC score to risk-stratify patients with suspected immune thrombotic thrombocytopenic purpura (iTTP) could lead to significant cost savings. Our consortium consists of institutions with an unrestricted approach to ADAMTS13 testing (Group A) and those that require pre-approval by the transfusion medicine service (Group B). Institutions in Group A tested more patients than those in Group B (P < 0·001) but did not identify more cases of iTTP (P = 0·29) or have lower iTTP-related mortality (P = 0·84). Decision tree cost analysis showed that applying a PLASMIC score-based strategy to screen patients for ADAMTS13 testing in Group A would have reduced costs by approximately 27% over the 12-year period of our study compared to the current approach. Savings were primarily driven by a reduction in unnecessary therapeutic plasma exchanges, but lower utilization of ADAMTS13 testing and subspecialty consultations also contributed. Our data indicate that using the PLASMIC score to guide ADAMTS13 testing and the management of patients with suspected iTTP could be associated with significant cost savings.     

Surgery for borderline tumor of the ovary

The five-year survival for women with Stage I borderline tumors is about 95% to 97%, but because of late recurrence the 10-year survival is only 70% to 95%. The five-year survival for Stage II-III patients is 65% to 87%. A more correct staging procedure, classification of true serous implants, and agreement on how the presence of gelatinous ascites in mucinous tumors contributes to cancer stage might change the distribution of stage and survival data by stage for women with borderline tumors in the future. Independent prognostic factors for patients with borderline tumors without residual tumor after primary surgery are: DNA ploidy, morphometry, International Federation of Gynecology and Obstetrics (FIGO) stage, histologic type, and age. Different types of surgery and chemotherapy were not independent prognostic factors. Questions which should be addressed include the following: 1) Have patients with borderline tumors been over treated in general, and how should these patients be treated? 2) In which group of patients is fertility-sparing surgery advisable? 3) Do patients with borderline tumors benefit from adjuvant treatment? And 4) How is the high-risk patient defined?     

A phase IB clinical and pharmacokinetic study of the angiogenesis inhibitor SU5416 and paclitaxel in recurrent or metastatic carcinoma of the head and neck

Purpose SU5416 is a novel small organic molecule that non-competitively inhibits the phosphorylation of the VEGF tyrosine kinase receptor, Flk-1. This phase IB study was performed to determine the safety, pharmacokinetics, and preliminary efficacy of the combination of SU5416 and paclitaxel in recurrent or metastatic carcinoma of the head and neck.Methods Enrolled in the study were 12 patients with biopsy-proven recurrent or metastatic carcinoma of the head and neck. Six patients received intravenous SU5416 110 mg/m² on days 1, 15, 18, 22 and 25, and paclitaxel 70 mg/m² on days 8, 15 and 22. Since two patients experienced a dose-limiting toxicity (DLT) in cohort 1, the next six patients received identical treatment as above except the paclitaxel dose was reduced to 55 mg/m² per week.Results A total of 42 cycles at two different dose levels were given. In cohort 1 there were two deep venous thromboses that were DLTs. In the second cohort there was a DLT consisting of a transient ischemic attack after receiving SU5416. Most of the other toxicities seen were grade 1 or 2 in nature and consisted of headache, facial flushing, and fatigue. Two patients developed extensive ulcerative cavities at sites of prior radiation. There were no significant changes in the pharmacokinetic parameters of SU5416 given with paclitaxel. Four patients had prolonged freedom from progression of 18, 28, 42, and 60 weeks duration.Conclusions The combination of SU5416 with paclitaxel had a higher than expected incidence of thromboembolic events and prophylactic anticoagulation should be considered for future trials that combine an angiogenesis inhibitor with cytotoxic chemotherapy. Although the future development of SU5416 as a chemotherapeutic agent is unclear, there was a clinical benefit seen with this combination in 36% of the patients. This trial supports the use of developing antiangiogenic combinations, using molecular targeted agents, in head and neck carcinoma.     

Prevention and management of severe intra-operative and post-operative bleeding in gynaecologic surgery

Severe intra-operative and post-operative bleeding is a potentially life-threatening complication of gynaecologic surgery. A sound clinical judgement and the adequate assessment and preparation of the patient are the best pre-operative means to avoid its occurrence. Intra-operative prevention requires knowledge of surgical anatomy and haemostatic techniques. The management of haemorrhagic complications can be extremely challenging. Its success depends on the perfect integration of surgical expertise, the supporting role of the anaesthesiologist and on the availability of a fully equipped interventional radiology team with much experience. A methodical and stepwise surgical approach is needed to selectively dissect and identify the bleeding site without damaging adjacent structures. In case of more diffuse or massive bleeding, the performance of a bilateral ligation of the anterior branch of the internal iliac arteries at an early stage is an appropriate measure. The anaesthesiologist is responsible for the maintenance of the patient’s haemodynamic function and the prevention of coagulopathy. Compression or atraumatic clamping of the aorta or placement of a pelvic packing can be temporarily applied to stabilize the patient’s condition. Only once this is achieved, can the subsequent option of angiographic arterial embolisation be considered.     

Anatomic variations of the inferior oblique muscle: a potential cause of failed inferior oblique weakening surgery

PURPOSE: To document the variations in normal anatomy that occur at the insertion of the inferior oblique muscle and in the vicinity of its surgical capture site (10 to 12 mm from the insertion). METHODS: One hundred intact cadaver orbits with no history of eye muscle or orbital disorders during life were carefully dissected to expose the entire length of the inferior oblique muscle. The number of divisions of muscle at the insertion, total width of the muscle belly, and variations in anatomy 10 and 12 mm from the insertion were recorded. RESULTS: Seventeen (17%) of the 100 inferior oblique muscles had multiple divisions at the insertion. Eight muscles (8%) had two bellies at 10 or 12 mm from the insertion. Among these eight, four had two distinct (bifid) bellies extending to the insertion, and four had dehiscences in the muscle. The mean muscle width among these eight specimens was 0.5 and 0.7 mm larger than the mean width of the other 92 specimens at the 10 mm and 12 mm positions, respectively. Neither difference was significant at the .05 level. CONCLUSIONS: Multiple insertions were found in 17% of inferior oblique muscles examined; duplications of the inferior oblique muscle at the surgical capture site were found in 8%. These duplications may account for some cases of recurrence or persistence of inferior oblique overaction after weakening surgery, owing to inadvertent incomplete capture of the muscle during surgery.     

A case report of unusual complication of myomatous uterus in pregnancy: spontaneous perforation of myoma after red degeneration

An unusual complication of myomatous uterus in pregnancy is presented. It shows spontaneous perforation of a myoma after red degeneration, presenting as an acute abdomen. To our knowledge spontaneous perforation of a necrotising leiomyoma has not been reported earlier. A review of the literature is given.     

Brain-derived neurotrophic factor (BDNF) gene delivery into the CNS using bone marrow cells as vehicles in mice

This study investigated the behavioral mechanisms underlying the anxiogenic, or anxiolytic mediated effects of CCK(2) receptor mediated agonist (CCK-4) and antagonist drugs (LY225910, LY288513, CR2945) in PVG hooded and Sprague-Dawley (SD) rats using the elevated plus maze test apparatus. In addition, the effects of a CCK(1) antagonist (CR1409) were investigated for its possible mediation in anxiety behavior between PVG hooded and SD rats. PVG hooded rats treated with CCK-4, decreased the time spent in the open arm and increased the time spent in the closed arm and correspondingly showed increase in the number of entries in the open arms while the number of entries in closed arm was insignificant, whereas SD rats decreased the time spent in the closed arm, while other parameters remained insignificant. PVG hooded rats administered with various CCK(2) antagonists (LY225910, LY288513, and CR2945) significantly increased the time spent in the open arm and correspondingly decreased the time spent in the closed arm, while the number of entries in the open or closed arm was insignificant, in contrast, SD rats failed to show any reliable significance. PVG hooded rats administered with the CCK(1) antagonist (CR1409), failed to show any reliable significance, in contrast, SD rats significantly increased the time spent in the open arm. The strain differences observed in this study suggests that CCK plays mainly as a neuromodulator, in which the various CCK(2) antagonists may not affect baseline anxiety state, but instead they modulate heightened states of anxiety through differential effects of CCK(1)/CCK(2) receptors.