Sickle cell 'girdle syndrome' progressing to ischaemic colitis and colonic perforation.

Abdominal pain of presumed vasocclusive origin, often termed 'girdle syndrome' because of the circumferential distribution of the pain, is common in sickle cell anaemia (SCA). Evidence of progression to bowel infarction is rare. A 27-year-old man with SCA developed chest and abdominal pain unresponsive to opiate analgesia. Abdominal X-ray showed dilated bowel loops because of partial obstruction. Despite reduction of HbS to 23% by automated red cell exchange, abdominal pain worsened. A CT scan was the most informative investigation and showed free peritoneal air. He underwent emergency hemicolectomy and reversible ileostomy formation. Histology of the resected colon was consistent with acute ischaemic colitis. Early surgical intervention remains essential in SCA when abdominal pain does not respond to maximal therapy including red cell exchange: as this case illustrates, sickle girdle syndrome has the capacity to progress to irreversible ischaemic colitis and necrotic perforation of the bowel wall.

A population study to define the incidence and survival of multiple myeloma in a National Health Service Region in UK.

Epidemiology data on multiple myeloma (MM) occurrence and outcome is inconsistent whilst a major limitation of randomized controlled trials is selection bias. We present a population-based analysis of patients diagnosed with MM in the South Thames area, which comprises 5.4 million adult inhabitants. A total of 855 cases of MM were ascertained between 1999 and 2000 in a collaborative project involving haematologists and the Thames Cancer Registry. The age-standardized rate was 3.29 per 100 000 and 4.82 cases per 100 000 (World Standard and European Population respectively). The median age was 73 years. The median survival for the whole group was 24 months whist it was 42 and 18 months in those aged less than 65 years and greater than 65 years respectively (P < 0.001). This population study has shown a higher incidence than previously reported in the UK and Europe and provides a benchmark for future studies. If survival is to be improved, future clinical trials and health care planning should consider patients over 65 years of age.

Platelet pheresis is not a useful adjunct to blood-sparing strategies in cardiac surgery.

OBJECTIVE: To examine whether specific platelet pheresis (minimal plasma harvested) would contribute toward reduced blood loss and allogenic blood requirements after cardiac surgery. DESIGN: A prospective randomized trial. SETTING: A large cardiothoracic surgical center. PARTICIPANTS: Consenting patients undergoing routine coronary artery or valve surgery (n = 54). INTERVENTIONS: Patients in the pheresis group underwent platelet pheresis in the anesthetic preparation room before general anesthesia. Pheresed platelets were stored during cardiopulmonary bypass and were returned to the patients after reversal of heparin with protamine toward the end of surgery. Control patients underwent their operations without this intervention. MEASUREMENTS AND MAIN RESULTS: Primary endpoints were blood loss and transfusion requirements. There were no differences between the 2 groups (pheresis v control: median loss, 960 mL v 1100 mL, p = 0.15; median blood transfused, 896 mL v 635 mL, p = 0.71). Secondary endpoints included analysis of platelet counts, platelet function, and surface markers. Counts remained the same after retransfusion of platelets up to 2 hours after surgery. Platelet aggregation to ristocetin was well preserved, but adenosine diphosphate caused almost no aggregation of the harvested platelets. Flow cytometry revealed the platelets to have a reduced surface density of the glycoprotein 1b receptor, and 13% of them were irreversibly activated. CONCLUSION: Platelet pheresis activates a proportion of the harvested platelets and impairs the function of the remainder; this may explain its failure to reduce postoperative blood loss and transfusion requirements.

Thromboelastography: a reliable test?

The thromboelastograph (TEG), a measure of global haemostasis, is routinely used during cardiac and hepatic surgery to optimize blood product selection and usage. It has recently been suggested that it may also be a useful tool to screen patients with hypercoagulable states. Limited published data on performance characteristics has led to speculation regarding its consistency and, therefore, validity of the results. This study was designed to assess the effect of stability of blood samples prior to testing, repeated sampling, intra- and inter-assay variability using the native, celite, tissue factor (TF) and Reopro-modified TEG. Analysis of native and celite samples after storage over 90 min showed a period of instability up to 30 min. Thereafter, all parameters between 30 and 90 min were stable [P = not significant (NS)]. When the same sample was repeatedly assayed, both native and celite TEG parameters showed a significant change towards hypercoagulability (P < 0.01), whereas the TF and Reopro-modified TEG showed no change. Intra- and inter-assay variability on samples tested after 30 min showed excellent reproducibility for all parameters (P = NS). The data suggest that the TEG is a useful tool in haemostasis but requires a formal standard operating procedure to be adopted that takes into account the initial period of sample instability.

The effect of treatment with Campath-1H in patients with autoimmune cytopenias.

We describe 21 patients with severe and life-threatening autoimmune cytopenias resistant to standard immunosuppression who were treated with the monoclonal antibody Campath-1H. Four patients had autoimmune neutropenia, four had autoimmune haemolytic anaemia, four had pure red cell aplasia, one had immune thrombocytopenia purpura (ITP), three had autoimmune haemolytic anaemia and ITP (Evan's syndrome), three had autoimmune pancytopenia (ITP, autoimmune neutropenia and autoimmune haemolytic anaemia), one had ITP (associated with acquired Glanzmann's disease) and autoimmune neutropenia, and one had ITP and red cell aplasia. Campath-1H was administered at a dose of 10 mg/d as an intravenous infusion for 10 d. Responses were seen in 15 patients, which were sustained in six. Relapse occurred in eight patients after Campath-1H treatment. Patients entering the study later, received cyclosporine after Campath-1H in an attempt to reduce the incidence of relapse. Three patients received a second course of Campath-1H; all responded but later relapsed. Fourteen patients are alive at a median of 12 months (range 4-61) after Campath-1H. Campath-1H represents an alternative therapeutic option for severe, refractory autoimmune cytopenias.

Red cell exchange, erythrocytapheresis, in the treatment of malaria with high parasitaemia in returning travellers.

In severe falciparum malaria with high parasitaemia, removal of parasitized erythrocytes is generally considered to be of value as adjunctive therapy in addition to standard chemotherapy. Such removal is commonly achieved by exchange transfusion but this procedure is time-consuming and may be associated with haemodynamic disturbance. Current-generation automated cell-separator hardware and software allows prompt red cell exchange, erythrocytapheresis, in a single continuous-flow isovolaemic procedure. We describe the application of this procedure to 5 cases of severe falciparum malaria in travellers returning to the UK from the tropics. All patients also received quinine and conventional supportive therapy. In all cases, dramatic reduction in parasitaemia was achieved within 2 h with subsequent complete clinical recovery. Erythrocytapheresis has significant advantages over exchange transfusion in terms of speed, efficiency, haemodynamic stability and retention of plasma components such as clotting factors and may thus represent an improvement in adjunctive therapy for severe malaria.

Amiodarone-induced bone marrow granulomas.

Amiodarone hydrochloride, a class III antiarrhythmic agent used to treat supraventricular and ventricular cardiac dysrhythmias. In this report we describe two patients receiving amiodarone for atrial fibrillation who underwent bone marrow biopsies to investigate paraproteinaemia (case 1) or severe thrombocytopenia (case 2). Multiple bone marrow granulomas were found in both patients, without evidence of any other cause. In both patients the granulomas disappeared after amiodarone withdrawal, suggesting a direct association.

Automated erythrocytapheresis in the treatment of severe falciparum malaria.

Removal of parasitized erythrocytes is generally considered to be of value as adjunctive therapy in severe falciparum malaria with high parasitaemia. This is commonly achieved by exchange transfusion. We describe three cases of severe falciparum malaria treated by automated erythrocytapheresis (red cell exchange) in addition to quinine and conventional supportive therapy. Erythrocytapheresis consists of removal of the red-cell fraction by apheresis. Plasma, leukocyte and platelet fractions are returned to the patient. In all cases, dramatic reduction in parasitaemia was achieved within 2 h with subsequent complete clinical recovery. Erythrocytapheresis has significant advantages over exchange transfusion in terms of speed, efficiency, haemodynamic stability and retention of plasma components such as clotting factors and may thus represent an improvement in adjunctive therapy for severe malaria.

Automated red cell exchange in sickle cell disease.

Red cell exchange is important in the care of acutely ill sickle-cell patients, and may be life-saving. An automated red cell exchange technique has been developed using a Baxter blood cell separator, enabling an isovolaemic exchange to be performed within 2.5 h. A total of 20 procedures have been performed in 15 patients, including one woman in the third trimester of pregnancy, with a mean decrease of 72% in the circulating sickle haemoglobin (HbS) level. This method enables almost all adult patients with sickle cell anaemia to have their HbS reduced to safe levels by only one procedure. The procedure was well tolerated by all patients, including those who were acutely ill. This technique provides an effective procedure for reducing the percentage of circulating HbS rapidly in acutely ill patients with complications of sickle cell anaemia.

Hypercoagulable abnormalities and postoperative failure of arterial reconstruction.

OBJECTIVES: To determine whether preoperative hypercoagulable abnormalities are independent risk-factors for the failure of arterial reconstruction in leg ischaemia. METHODS: Sixty consecutive patients were studied before, and for 1 year following, elective peripheral revascularisation. Antithrombin III, protein C and protein S levels, and tests for lupus anticoagulant were performed preoperatively, and then repeated on the first and third postoperative days and after 1 and 6 months. Heparin-associated thrombocytopenia was also investigated if there was a postoperative fall in platelet count greater than 100 x 10(9)/l. RESULTS: Forty-six (77%) procedures were performed for critical ischaemia and 15 (25%) involved infrapopliteal reconstruction. The nature of surgery or accepted risk factors for occlusion were comparable between the 40 (67%) patients with patent reconstructions at 1 year and the 20 (33%) who had suffered failure. Preoperative hypercoagulable abnormalities were detected in 21 (35%) patients, with a three times greater incidence in those whose reconstructions failed (65% vs. 20%, p < 0.01), and in 11 of 12 patients suffering early (within 1 month) occlusion. The lupus anticoagulant was more frequently detected when prosthetic grafts were already present (p < 0.05) and carried a positive predictive value for reocclusion of 67% (p < 0.01). All three postoperative deaths occurred in patients with low protein S levels before surgery. CONCLUSIONS: Hypercoagulable abnormalities are common prior to arterial revascularisation and are independently associated with subsequent failure.

Circulating villous lymphocytes--a link between hyperreactive malarial splenomegaly and splenic lymphoma.

Significant numbers of villous lymphocytes were noted in the blood of patients with a clinical diagnosis of hyperreactive malarial splenomegaly (HMS) in Ghana. Demographic and haematological data were recorded from 22 patients with massive splenomegaly. Additional investigations included lymphocyte immunophenotyping, protein electrophoresis and immunoglobulin gene rearrangements. Although all patients had over 30% villous lymphocytes and no leucocytosis, 7 had no evidence of a monoclonal disorder. Immunophenotyping and the presence of monoclonal lymphocytes identified 3 further patients with B-cell splenic lymphoma with villous lymphocytes (B-SLVL). HMS and SLVL co-existed in the same, predominantly female, patient population and were indistinguishable except by molecular analysis of lymphocytes. The discovery of the uncommon villous lymphocytes in both non-malignant and malignant disorders in the same geographical area suggested that HMS and SLVL are pathophysiologically related. In Caucasians with SLVL the malignant cells arise from B-cells that have undergone antigen selection. We postulate that the excessive proliferation of polyclonal B-lymphocytes, driven by frequent exposure to malaria, predisposes to the emergence of a malignant lymphoma, B-SLVL, in tropical West Africa.

Comparison of immunofiltration assay of plasma D-dimer with diagnostic imaging in deep vein thrombosis.

This prospective study was designed to assess the diagnostic sensitivity, specificity and negative predictive value of the NycoCard D-dimer plasma immunofiltration assay in patients with suspected deep vein thrombosis (DVT) confirmed by ultrasonography/venography. 84 medical patients were recruited: 43 patients (51%) had proven venous thrombosis, 33 by venography and 10 by ultrasonography. The sensitivity of NycoCard D-dimer in patients with DVT was 95.3%, the specificity was 22.0% and the negative predictive value was 81.8%. An algorithm including the NycoCard D-dimer test for the acute management of DVT is proposed. This would enable low-risk patients to be discharged early from hospital, without imaging or anticoagulant therapy.

Lymphocyte responses to human cytomegalovirus in different groups of patients in Britain and in adults from west Africa and the Middle East.

Antibody prevalence and lymphocyte proliferation responses to cytomegalovirus (CMV) and herpes simplex virus (HSV) were compared in several different groups of patients: genitourinary medical (GUM) patients, hemophiliacs, men with clinical acquired immunodeficiency syndrome (AIDS) and cases of primary CMV mononucleosis, and also in adults in the general population (control subjects) comprising separate groups native to Britain, West Africa, and the Middle East. Among the British control subjects who were positive for CMV IgG, all were also positive against CMV antigen by the lymphocyte transformation test (LTT). However, among those who were CMV IgG-positive in the various groups of patients, 20-86.9% gave positive responses to CMV antigen by the LTT; moreover, 75.7% and 55.5% of the CMV IgG-positive healthy control subjects from West Africa and the Middle East, respectively, gave positive LTT responses to CMV antigen. When the same groups of patients were tested for responsiveness to HSV antigen by the LTT, there was good agreement between a positive result by this test and by serology in all except those with primary CMV mononucleosis (42.8%). Overall, lymphocyte responses to CMV were significantly impaired in healthy, CMV antibody-positive subjects from West Africa and the Middle East compared to similar subjects from Britain.

Trousseau's syndrome in association with ovarian carcinoma.

BACKGROUND: The association of neoplastic disease and thromboembolic disorders was first recognized by Trousseau in 1865. Abnormalities of blood coagulation tests have been reported in the majority of patients with cancer, including ovarian carcinoma. However, Trousseau's syndrome has rarely been reported in women with ovarian carcinoma. METHODS: A literature search for cases of Trousseau's syndrome in association with ovarian carcinoma was performed using the MEDLINE database. Case notes of patients with ovarian carcinoma treated at St. George's Hospital were reviewed and cases of Trousseau's syndrome identified. RESULTS: We report a series of 4 cases of Trousseau's syndrome in association with ovarian carcinoma occurring over a 3- to 4-year period, and highlight the particular difficulties associated with the management of these thromboembolic effects. CONCLUSIONS: Trousseau's syndrome can impair quality of life in patients with advanced ovarian carcinoma and enhanced anticoagulation regimens may be required for effective palliation.