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Awareness of deep venous thrombosis has increased considerably in the last decade including recognition of the importance of thromboprophylaxis for acutely ill hospital inpatients as preventative therapy. Combinations of a pre-test probability score plus a D-Dimer analysis can identify those patients where the chances of DVT are very low and radiological investigation can be obviated. The gold standard for diagnosis is still either ascending venography or venous Doppler ultrasound. Low molecular weight heparin has taken over from unfractionated calcium heparin as the initial treatment of choice. There are many challenges in management, especially deciding the optimum duration of anticoagulant treatment in order to balance the risks of drug induced bleeding against recurrent venous thromboembolic events.

We report the case of a 45-year-old man who was diagnosed in June 1969 9 years old as having mild haemophilia A following a traumatic left shoulder bleed when his factor VIII (FVIII) activity was 11 IU dL(-1) based on a two-stage assay. The bleed resolved following treatment with intravenous cryoprecipitate. There was no family history of haemophilia. Cryoprecipitate infusions were required to treat further traumatic bleeds between 1971 and 1981. During this time, his FVIII activity was confirmed at 14 IU dL(-1). He defaulted many hospital appointments until 1991 when his FVIII activity had risen to 42 IU dL(-1). There was no evidence of infection, inflammatory or liver disease to account for this change. By 2005 he had a normal FVIII activity of 62 IU dL(-1) based on a one-stage assay. FVIII gene analysis confirmed a codon 531 mutation. It appeared that the discrepant FVIII results related to whether a two-stage or one-stage assay was used that has been previously reported for other patients with these mutations. We felt it important to raise awareness that this phenomenon may lead to apparent correction of haemophilia A.

We report the case of a 71-year-old man on warfarin for chronic atrial fibrillation presenting with a massive spontaneous soft tissue bleed. Despite reversing the effects of warfarin with large doses of intravenous vitamin K and fresh frozen plasma, bleeding continued, and his prothrombin time and activated partial thromboplastin time remained prolonged. The prothrombin time and activated partial thromboplastin time failed to correct with 50% normal plasma. Further investigations confirmed a lupus inhibitor with low levels of factors II, V, VII and XI. Factor II, V and XI levels normalized, however, when the patient's plasma was diluted 1:16 in buffer, suggesting the lupus inhibitor may have been interfering with these factor assays causing artefactual low results. Factor VII levels remained consistently low at all dilutions. The patient subsequently died following a massive left haemothorax despite surgical intervention and treatment with activated recombinant factor VII concentrate. We presumed the primary problem was bleeding from a local vascular lesion but the patient was never well enough to undergo confirmatory angiography. This case highlights the fact that patients with lupus inhibitors can develop severe haemorrhagic complications, and illustrates the complexities involved in both the investigation and treatment of abnormal bleeding in these patients.

We report the case of an 8-year-old boy with no prior abnormal bleeding history who presented with severe central abdominal pain following a freak accident at a local ice rink. Clinical examination confirmed a tender periumbilical mass. An ultrasound scan confirmed a large haemorrhagic fluid collection adjacent to the second part of his duodenum that was causing a subacute small-bowel obstruction. He was found to have a persistently prolonged prothrombin time between 17.3 and 18.1 s but normal liver function tests. There was no suggestion of dietary vitamin K deficiency. Further investigations confirmed factor VII deficiency with levels between 30.4 and 33.6 IU dL-1. His prothrombin time did not normalize with intravenous vitamin K. He was subsequently treated with three 30 microg kg-1 body weight doses of novoseven at 4-h interval and made an excellent recovery. The haematoma virtually resolved completely confirmed by a follow-up ultrasound scan 3 months after the initial event.

We report the case of a 72-year-old lady who presented with fatigue and bruising. Initial investigations were compatible with iron deficiency anaemia and idiopathic thrombocytopenic purpura (ITP). The anaemia and recent heartburn symptoms led to endoscopy, which revealed an extensive oesophageal squamous cell carcinoma. The tumour was inoperable due to local extension and the patient was not deemed fit enough for aggressive chemotherapy. A course of radical local radiotherapy was given. The patient's ITP, which had initially been responsive to high-dose intravenous immunoglobulin, subsequently became refractory to all therapeutic modalities. The patient developed significant dysphagia but therapeutic options were limited due to her severe thrombocytopenia. The patient eventually died from a combination of gastrointestinal and intrapulmonary haemorrhage. This case is of interest for two reasons. First, the development of refractory ITP appeared to mirror the progression of the carcinoma, and to our knowledge this is the first case of ITP associated with oesophageal carcinoma. Second, despite recent endoscopic advances in palliating oesophageal tumours, this case highlights the difficulties that can still occur.

Standard treatment for patients with metastatic colorectal carcinoma (MCC) involves treatment with weekly 5-flurouracil (5-FU) chemotherapy by continuous infusion, requiring the insertion of a central venous catheter (CVC). One of the main complications of CVCs is venous thromboembolic disease (VTE), with an incidence varying between 3 and 54% in different studies. During the past 14 months, 17 patients with MCC have been treated weekly with 5-FU in our unit, comprising 11 males and six females with a mean age of 60 years (range, 49-72 years). Thromboprophylaxis for all patients included 1 mg/day warfarin unless contraindicated. Three patients developed venography-confirmed CVC-related VTE, including two cases of occlusive superior venocaval VTE. All three patients were treated with intravenous thrombolytic drugs; two responded completely and one partially. We wonder whether the incidence of CVC-related VTE may be reduced further by using adjusted-dose warfarin rather than fixed low-dose warfarin. However, one has to be guarded because of the greater risk of bleeding with more intensive anticoagulation, especially in patients with liver metastases. Ongoing studies such as the warfarin prophylaxis study are essential to determine the safety and efficacy of different approaches in order to determine the optimum thromboprophylaxis for this group of patients.

We present the case of a patient diagnosed as having presumed idiopathic thrombocytopenic purpura (ITP) who subsequently developed chronic myelomonocytic leukaemia (CMML) after an interval of 16 months. A variety of peripheral cytopenias are commonly seen in myelodysplastic disorders (MDS), and autoimmune phenomena, including secondary ITP, are well described, especially in cases of CMML. We would advocate evaluation for possible MDS/CMML by morphological examination of the peripheral blood/bone marrow in adult patients presenting with isolated thrombocytopenia, especially if there is subsequent development of additional peripheral cytopenias, monocytosis or hepatosplenomegaly.

Hairy cell leukaemia (HCL) is a rare lymphoproliferative disorder associated with pancytopenia, splenomegaly and the presence of typical hairy B lymphocytes in the bone marrow and/or peripheral blood. The most significant complication relates to opportunistic infections that arise as a consequence of neutropenia and monocytopenia. HCL is occasionally associated with systemic autoimmune disorders including polyarteritis nodosa and rheumatoid disease. Secondary autoimmune haemolytic anaemia (AIHA) appears to be rare. We report on two cases of HCL complicated by fatal cold anti-i AIHA. Fulminant haemolysis causing death is rare in cold AIHA and only a few individual cases have been reported, none having anti-i specificity.

The prothrombin gene mutation, 20210A, a guanine to adenine substitution at nucleotide position 20210, has recently been described as an additional risk factor for venous thromboembolic disease. We describe the case of a patient with combined heterozygous prothrombin 20210A mutation and type 1 protein C deficiency who presented with massive mesenteric venous infarction of his small bowel and survived following the use of protein C concentrate and extensive small bowel resection.

We report a case of traveller to Kenya who contracted severe plasmodium falciparum malaria complicated by disseminated intravascular coagulation and acute renal failure. She had taken no antimalarial prophylaxis in view of concerns in the media regarding the adverse effects of mefloquine. There was a protracted delay before the diagnosis of malaria was made. Clinical recovery occurred following treatment with intravenous quinine, haemofiltration and manual/automated red-cell exchange transfusions. Automated red-cell exchange transfusion resulted in a marked decrease in the parasitaemia, before a response to quinine therapy would have been anticipated, leading to a successful outcome thereafter. In conjunction with other groups we therefore feel that exchange transfusions should be considered in seriously ill patients with falciparum malaria, multiorgan complications and parasitaemias greater than 10%.

We have investigated monocyte function in 30 patients with lymphoplasmacytic disorders and in 21 age and sex matched normal controls. Marked abnormalities of all facets of monocyte function were demonstrated in six patients with multiple myeloma (MM) and a single patient with Waldenström's macroglobulinaemia (WM) plus significant paraproteinaemia. Serious infection occurred in three of these patients. An inverse relationship between the level of the serum paraprotein and impairment of monocyte phagocytosis plus killing of Candida albicans was observed. Crossover studies suggested that these abnormal findings were constitutive and not reversed by removal of the serum paraprotein. The data suggest that monocyte function is constitutively abnormal in patients with MM and can be further, but reversibly, inhibited by high paraprotein levels. Further research is required to confirm these findings, ascertain whether monocyte function can be normalized using chemotherapy or growth factors, and if so, whether their tumouricidal functions could be harnessed in the treatment of this currently incurable condition.

This study was undertaken in 102 adult patients to evaluate the safety and efficacy of intravenous (i.v.) midazolam in the setting of bone marrow aspiration and trephine biopsy (BMAT). Combined local anaesthetic (LA) and sedation was used in 87% of patients and 13% received LA alone. Amnesia occurred in all sedated patients with only 9% experiencing a mild degree of post-procedure pain. This contrasted sharply with the non-sedated group, in whom 85% had intense pain during the biopsy followed by protracted local discomfort in approximately 54%. Drowsiness and some psychomotor impairment were the only notable sedation-related side-effects in approximately 20%. None required assisted ventilation. There was a resounding patient preference for BMAT with sedation. Considering the ease of use, safety and efficacy of i.v. midazolam, the availability of flumazenil as a reversal agent and the undoubted positive effects on quality of life, we would advocate using it in BMAT provided that there were no contraindications.