Hyperplasia and the degree and activity of inflammation in chronic recurrent tonsillitis: a histopathological study.

Postoperative haemorrhage following tonsillectomy occurs in 5.98% of all cases with up to 10 deaths reported annually in Germany. When comparing tonsillectomy (TE) and tonsillotomy (TT), the same long-term frequency of ENT infections is displayed in children and young adults. However, taking postoperative haemorrhaging into account, TT is more favourable. Chronic tonsillitis is one of the most common indications for TE in the adult population; however, a histopathological characterization may reveal objective criteria and provide a foundation for routinely performing TT in adults too. Three essential parameters hyperplasia (HP), grade of inflammation (GOI) and activity of inflammation (AOI), which are responsible for, and associated with a clinically relevant disease were histopathologically examined in the tonsils of 100 adult patients with chronic recurrent tonsillitis. The parameters were analysed and compared separately in the pharyngeal and basal parts of the tonsils as well as in three sections (upper and lower pole of the tonsil, middle part) as this may influence the indication for TT. The comparison of the basal and pharyngeal portions displayed a significant difference in the GOI and the HP in all three sections: grade 2 HP as well as GOI were more commonly found in the basal than pharyngeal portions (p > 0.001). AOI (grade 2) displayed the same properties in the middle section (p < 0.002), but did not reach statistical significance in the cranial and caudal sections (p = 0.107 and p = 0.186). An overabundance of grade 1 GOI, AOI, and HP was seen in the pharyngeal sections. The results show that two out of three relevant parameters that demonstrate histopathological changes in recurrent inflamed tonsils have a significantly stronger presence in the basal section of the tonsil as opposed to the pharyngeal section. The processes initiated by inflammation next to the surface responsible for a clinically relevant recurrent tonsillitis seem to cause stronger reactions in the deep follicular portion of the tonsils.

Anti-HLA alloantibodies in surgical patients refractory to platelet transfusion.

Alloimmune platelet refractoriness (alloPR) among actively bleeding surgical patients with thrombocytopenia represents a life-threatening problem. Here we present three cases in which surgical bleeding was complicated by life-threatening thrombocytopenia and alloPR. We demonstrate that the human leukocyte antigens (HLA) antibodies associated with alloPR are broadly reactive and in high concentration, are not removed by hemodilution, and are not absorbed by transfusion of multiple doses of platelet concentrates. HLA alloPR may be under-recognized among surgical patients. Research is needed to develop pre-operative screening methods that will identify patients in need of specialized platelet support using HLA compatible donor products.

Immune-mediated coagulopathy associated with topical bovine thrombin: review of the pediatric literature.

Postoperative bleeding may occur from a number of etiologies. An uncommon cause of postoperative bleeding is immune-mediated coagulopathy resulting from reexposure to a topical hemostat containing bovine thrombin. Some patients may develop antibodies to bovine thrombin (and other bovine coagulation proteins present in the product) which cross-react with human coagulation proteins, resulting in a coagulopathy, and occasionally, in serious bleeding and death. Most of the clinical information on this coagulopathy is in the adult medical literature. This article reviews the literature on pediatric cases with this coagulopathy and summarizes clinical outcomes and effective therapies.

Influence of red blood cell transfusion on CD4+ T-helper cells immune response in patients undergoing cardiac surgery.

BACKGROUND: Both surgical insult and red blood cell transfusion (RBCT) induce alterations in type-1/type-2, CD4T-helper cell balance. This study was aimed to determine the influence of RBCT on Th1 and Th2 function immune response in cardiac surgery patients. MATERIAL AND METHODS: Three blood samples were prospectively drawn from 81 cardiac surgery patients with cardiopulmonary bypass (CPB): preoperatively (preOP), during CPB, before RBCT (intraOP), and on postoperative day 1 (postOP). Immune response was assessed by flow cytometry measurement of the proportion of CD4(+)T-helper cells producing tumor necrosis factor (TNF)-α [Th1 response] and interleukin (IL)-10 [Th2 response]. RESULTS: Sixty-two patients were transfused (3.4 ± 2.3 units/patient), whereas 19 did not. Both groups were homogeneous, both at baseline and during surgery, regarding multiple perioperative clinical and laboratory variables, but postoperative blood loss and transfused RBC units were significantly higher in transfused versus nontransfused patients. In contrast, preoperative hemoglobin was significantly higher in nontransfused patients. CD4(+)T-helper cells significantly decreased in both groups of patients from preOP to intraOP 1 and from intraOP to postOP. In nontransfused patients, there were no significant changes in CD4(+)T-helper cells expressing TNFα or IL-10 among different sampling times. In contrast, RBCT resulted in a significant increment in Th2 response from intraOP to postOP (P=0.01), without affecting Th1 response. CONCLUSION: RBCT, but not surgery or CPB, induces a shift of the Th1/Th2 balance toward Th2 dominance.

The influence of the preoperative immune response on blood transfusion requirements in patients undergoing cardiac surgery.

OBJECTIVE: The purpose of this study was to evaluate the influence of preoperative type I and II immune responses on blood transfusion requirements. DESIGN: A prospective and observational trial. SETTING: A postcardiac surgery unit of a university hospital. PARTICIPANTS: Seventy-one consecutive patients undergoing elective cardiac surgery. INTERVENTIONS: Blood samples drawn for laboratory analysis and immunologic study. MEASUREMENTS AND MAIN RESULTS: Patients were divided into 2 groups according to blood transfusion requirements: < or = 2 units (n = 35) and >2 units of red blood cells (n = 36). The preoperative immune response was assessed by flow cytometry, measuring the proportion of CD4+ T helper cells producing cytokines, including Th1 response (interferon-gamma and tumor necrosis factor-alpha [TNF-alpha]) and Th2 response (interleukin 4 and 10). Two logistic regression analyses (including and not including immunologic variables) were used to select and weight perioperative variables associated with an increased risk of transfusion. Three variables were found to be independent predictors of transfusion requirements when immunologic variables were not included: preoperative platelet count, preoperative hemoglobin, and hypertension. When all the variables were included, preoperative hemoglobin, cardiopulmonary bypass time, and the preoperative proportion of CD4+ T cells producing TNF-alpha were associated with an increased risk of transfusion (Hosmer-Lemeshow, 0.33; c-index, 0.93), but preoperative platelet count and hypertension were not. CONCLUSIONS: A low preoperative Th1 immune response, as assessed by the proportion of CD4+ T-helper-producing TNF-alpha, was associated with a higher blood transfusion rate.

Postoperative hemorrhage caused by portal hypertension associated with autoimmune pancreatitis: A case report.

RATIONALE: Autoimmune pancreatitis is a form of chronic pancreatitis, characterized by diffused enlargement of the pancreas and irregular narrowing of the main pancreatic duct. The theory that portal hypertension is associated with autoimmune pancreatitis has not been emphasized. In addition, only a few studies report that the gastrointestinal tract hemorrhage caused by portal hypertension is associated with autoimmune pancreatitis. PATIENT CONCERNS: The patient was a 61-year-old male with pancreas occupying lesion detected in a physical examination. Preoperative CT showed portal vein diameter increased significantly (1.6 cm) and the junction of splenic and portal vein was capsuled by lesions and the splenic vein became thin. The Whippie procedure was performed for the correction of the lesion. The pancreatic tissue showed chronic inflammation and lymphocytic infiltration and fibrosis, and abundant IgG4 cells. After the surgery, the patient suffered twice from postoperative hemorrhage (9 and 16 mos). DIAGNOSES: Postoperative hemorrhage, autoimmune pancreatitis. INTERVENTION: Electronic gastroscopy, exploratory laparotomy, and titanium clips were used simultaneously to stop the bleeding. OUTCOMES: The patient recovered well after the surgery. LESSONS: In this study, we present the case of repeated postoperative hemorrhage (9 and 16 mos). We discussed the correlation between postoperative hemorrhage and autoimmune pancreatitis, and the cause of postoperative hemorrhage.

Immunochemical analysis of polyspecific antibodies in patients exposed to bovine fibrin sealant.

BACKGROUND: Patients exposed to bovine thrombin preparations in fibrin sealant often develop antibodies to bovine coagulation proteins, which cause significant bleeding by cross-reacting with human homologues. Recipients of our left ventricular assist system (LVAS) routinely are exposed to fibrin sealant; therefore, we determined whether they developed antibodies. METHODS: We compared sera from 6 LVAS recipients exposed to fibrin sealant (THROMBOGEN, Johnson & Johnson, Arlington, TX ) during LVAS placement to that of 5 nonexposed LVAS recipients. Pre-LVAS and weekly post-LVAS sera were tested for immunoglobulin (Ig)G, IgA, and IgM reactivity to THROMBOGEN by enzyme-linked immunosorbent assay. Peak IgG and IgA reactive sera were characterized by immunoblotting. RESULTS: All patients exposed to THROMBOGEN developed antibodies: 5 developed IgG, 4 IgA, and 3 IgM. In contrast, nonexposed patients did not develop antibodies. Only some antibody reactivity was contributed by antithrombin or antifactor V antibodies. Silver stain sodium dodecyl sulfate-polyacrylamide gel electrophoresis analyses of THROMBOGEN showed more than 18 bands, many of which were recognized in Western blot by positive patient sera. CONCLUSIONS: We found both IgG and IgA polyspecific antibody responses in patients exposed to bovine thrombin preparations.

Risk and clinical significance of developing antibodies induced by topical thrombin preparations.

OBJECTIVE: TO determine the clinical relevance, prevalence, and risk of antibody development in patients exposed to topical bovine thrombin preparations. DESIGN: A prevalence study of individuals previously exposed to topical bovine thrombin was done by screening using Western blot assay to detect antibodies against bovine thrombin preparations. SETTING: A large tertiary care center. PATIENTS: A convenience sample of 120 stored blood specimens from patients previously exposed to topical bovine thrombin was identified from hospital records. A control sample of 114 stored blood specimens from nonexposed patients was used. Case reviews for 2 exposed patients with severe bleeding complications and difficult clinical management are presented. RESULTS: Twelve of the bovine thrombin-exposed patients were found to have antibodies directed against bovine thrombin and other coagulation factors (95% CI, 4.6%-15.4%). Patients receiving multiple exposures were 8 times more likely to develop antibodies than were patients with a single exposure (P < .001). CONCLUSIONS: (1) Topical bovine thrombin is associated with formation of antibodies to coagulation factors; (2) Patients receiving multiple exposures are more likely to develop antibodies to coagulation factors; and (3) Topical bovine thrombin use may cause severe bleeding problems and should be avoided if there has been previous exposure.

Postoperative bleeding in an elderly patient from acquired factor V inhibitor: rapid response to immunosuppressive therapy.

Acquired factor V inhibitor is a rare but potentially life-threatening hemorrhagic disorder caused by the development of autoantibodies directed against coagulation factor V. The management of acute bleeding and inhibitor eradication is the mainstay of the treatment. The authors report a case of a 79-year-old man who underwent right hip arthroplasty and postoperatively, when on Coumadin for deep venous thrombosis prophylaxis, developed bleeding from the surgical site with a hematoma and abnormal coagulation parameters. Further workup revealed an acquired factor V inhibitor. The approach to treat this rare and challenging disorder is discussed. The patient responded rapidly with disappearance of factor V inhibitor titers after initiation of treatment with rituximab, prednisone and cyclophosphamide.

Perigraft hemorrhage after abdominal aortic aneurysm repair in a heart transplant patient.

Spontaneous perigraft hemorrhage can occur years after a successful aortic aneurysm repair. Such hemorrhage can result, in part, from inadequate graft healing. Herein, we describe the case of a heart transplant recipient who underwent an abdominal aortic aneurysm repair that was complicated by an acute perigraft leak 6 weeks later. Apparently, suppression of the patient's immune system impaired proper healing of the graft-aortic anastomosis site. In patients who have a compromised immune system, an additional 4-0 polypropylene pledgeted suture line should be placed for reinforcement during abdominal aortic aneurysm repair. Postoperatively, patients who are given immunosuppressive therapy should undergo careful, long-term monitoring.

Inflammatory response and platelet activation after off-pump coronary artery bypass surgery.

BACKGROUND: Cardiac surgery induces a systemic inflammatory activation and alterations in the hemostatic cascade. The responses contribute to postoperative complications but may also have protective effects. We investigated the relationship between inflammation, hemostasis and bleeding after off-pump coronary artery bypass surgery (OPCAB). METHODS: Ten OPCAB patients were included in a prospective descriptive study. Selected markers of inflammation (IL-6, IL-8, PMN-elastase, C3a, and SC5b-9), and hemostasis (platelet count, ss-thromboglobulin, anti-thrombin, D-dimer and fibrinogen) were measured before and immediately after surgery. Postoperative bleeding was registered. RESULTS: Inflammatory variables did not alter significantly during surgery while ss-thromboglobulin concentrations increased and anti-thrombin and fibrinogen decreased. There were significant postoperative correlations between PMN-elastase and ss-thromboglobulin (r=0.82, p=0.004), between PMN-elastase and fibrinogen (r=0.69, p=0.03) and between C3a and ss-thromboglobulin (r=0.71, p=0.02). In addition, there were significant inverse correlations between postoperative bleeding and pre- and postoperative fibrinogen levels (r=-0.76, p=0.011 and r=-0.84, p=0.002 respectively), between bleeding and postoperative ss-thromboglobulin levels (r=-0.66, p=0.04) and between bleeding and postoperative PMN-elastase (r=-0.75, p=0.01). CONCLUSIONS: The results give further evidence for an association between the inflammatory response and hemostasis after cardiac surgery.

Surgery-associated acquired hemophilia A.

We present two patients who acquired factor VIII antibodies in the immediate postoperative period. One patient was receiving warfarin that was temporarily discontinued but reintroduced after the procedure. Preoperatively, none gave a history of bleeding, even with past surgeries, and both had normal coagulation tests. Within days of surgery, hemorrhage with prolonged activated partial thromboplastin time, low factor VIII levels, and demonstrable factor VIII antibodies were observed. For the patient who was receiving warfarin the severe bleeding was attributed, at the beginning, only to the high international normalized ratio (INR), which resulted in a fatal delay in diagnosis and appropriate treatment. We would like to raise awareness of surgery as a precipitating cause of acquired hemophilia, which is something to be considered with unusual postoperative bleeding. This syndrome is remarkable for its abrupt onset within days of surgery, severe bleeding but potential successful outcome with combined hemostatic control with recombinant activated FVII (rFVIIa) and elimination of the antibody by immunosuppression.

Apathetic Graves' disease and acquired hemophilia due to factor VIIIc antibody.

Acquired hemophilia due to autoantibody to Factor VIII coagulant (Factor VIIIc) is a rare event which may be observed in patients with different autoimmune diseases. To our knowledge, this association has been reported only once in patients with autoimmune thyroid disease. Here we describe a patient presenting with a severe hemorrhagic disorder due to Factor VIIIc antibody in whom biochemical screening for thyroid diseases led to a diagnosis of hyperthyroid Graves' disease not associated to overt clinical features. This case underlines the importance of carrying out a complete screening for autoimmunity, including thyroid autoimmune disease, in all patients with apparently isolated serum Factor VIIIc inhibitors.

Membrane attack complex contributes to destruction of vascular integrity in acute lung allograft rejection.

The lung is known to be particularly susceptible to complement-mediated injury. Both C5a and the membrane attack complex (MAC), which is formed by the terminal components of complement (C5b-C9), can cause acute pulmonary distress in nontransplanted lungs. We used C6-deficient rats to investigate whether MAC causes injury to lung allografts. PVG.R8 lungs were transplanted orthotopically to MHC class I-incompatible PVG.1U recipients. Allografts from C6-sufficient (C6(+)) donors to C6(+) recipients were rejected with an intense vascular infiltration and diffuse alveolar hemorrhage 7 days after transplantation (n = 5). Ab and complement (C3d) deposition was accompanied by extensive vascular endothelial injury and intravascular release of von Willebrand factor. In contrast, lung allografts from C6-deficient (C6(-)) donors to C6(-) recipients survived 13-17 days (n = 5). In the absence of C6, perivascular mononuclear infiltrates of ED1(+) macrophages and CD8(+) T lymphocytes were present 7 days after transplantation, but vascular endothelial cells were quiescent, with minimal von Willebrand factor release and no evidence of alveolar hemorrhage or edema. Lung allografts were performed from C6(-) donors to C6(+) recipients (n = 5) and from C6(+) donors to C6(-) recipients (n = 5) to separate the effects of systemic and local C6 production. Lungs transplanted from C6(+) donors to C6(-) recipients had increased alveolar macrophages and capillary injury. C6 production by lung allografts was demonstrated at the mRNA and protein levels. These results demonstrate that MAC causes vascular injury in lung allografts and that the location of injury is dependent on the source of C6.