Biomedical subjects
Publications and source records attributed to H G Watson.
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The production of clinical guidelines has become an accepted and lauded part of modern medicine. It is also widely perceived that these guidelines provide some sort of panacea for the problems that medicine faces. Our experience suggests otherwise. Triggered by on going anecdotal evidence of poor practice, we reviewed the effect on practice of a recently introduced local guideline on the management of major bleeding in patients on warfarin. Comparing 34 patients treated before and 48 patients after the introduction of the guideline, we found no significant improvement in prothrombin complex concentrate dosing or administration of vitamin K. The only improvement witnessed was in early assessment of the effect of the intervention on coagulation which improved from 10 to 35% of cases. Of major concern, in 10% of cases, there was no documentation to confirm or refute that prothrombin complex concentrate (PCC), which had been issued, had actually been administered to the patient. The production and widespread dissemination of this local guideline did not achieve significant improvement in clinical practice. Possible reasons for failure to adhere to the guideline are discussed.
The current literature suggests a weak association between long-distance travel and the development of asymptomatic venous thromboembolism (VTE). Most of the data available relate to air travel and suggest that the risk is largely confined to asymptomatic calf vein thrombosis in passengers with additional risk factors for VTE, travelling for more than 8 h. The risk of both symptomatic and fatal pulmonary embolism (PE) is very small. The causal role of travel-related factors (e.g. stasis, dehydration, cramped seats and hypobaric hypoxia) is not yet proved but, given the plausible risk-free benefit, all passengers should be advised to maintain adequate hydration and exercise. There is currently no evidence for 'routine' thromboprophylaxis using stockings or drugs. In passengers with additional risk factors for VTE, thromboprophylaxis in the form of below-knee graduated compression stockings (providing 15-30 mmHg at the ankle) and/or prophylactic dose low-molecular-weight heparin may be considered. The evidence does not support the use of aspirin, which is associated with a significant rate of adverse gastrointestinal effects.
There has been a significant increase in the amount of diagnostic testing performed to confirm or refute a diagnosis of deep-vein thrombosis (DVT), often in low-risk patients. D-dimer testing and computer-assisted strain gauge plethysmography (SGP) are rapid, inexpensive methods of excluding DVT and, in combination with a clinical probability score for DVT, both have been used to accurately exclude DVT. D-dimer testing, SGP and a combination of both in excluding DVT were compared in 243 ambulant outpatients who followed a prespecified investigation protocol. The negative-predictive value of D-dimer testing alone was 100%, 93.9% (95% CI 93.6-94.1) and 80% (95% CI 73.7-86.3) in patients with a low, moderate and high pretest probability (PTP) score for DVT respectively. The corresponding results for SGP were 95.6% (95% CI 95.5-95.7), 86.1% (95% CI 85.9-86.4) and 77.8% (95% CI 75.9-79.7) in patients with a low, moderate and high PTP score for DVT respectively. D-dimer testing provided a rapid, cost-effective method for excluding DVT in low-risk ambulant patients, which was superior to SGP. Combined use of the modalities did not improve any aspect of clinical decision making.
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Anaemia may result in tissue hypoxia which may induce or exacerbate symptoms of ischaemia. Tissue hypoxia may however also result from the presence of haemoglobin with altered oxygen-binding characteristics. Drug-induced methaemoglobinaemia in which oxygen is irreversibly bound to haemoglobin may complicate the use of some common drugs. This condition may result in severe tissue hypoxia, which is rapidly and cheaply reversed by methylene blue.
The immunization of patients with bleeding disorders differs from that of the normal population with respect to the risk of haematoma formation at the vaccination site and the unusual infective risks associated with the potential, and past, exposure to blood products. Most vaccinations can be given subcutaneously and this should be the preferred route. All routine childhood vaccinations should be given at the appropriate time. All patients with bleeding disorders should be vaccinated against hepatitis A and B. HIV positive patients should receive annual influenza vaccinations and should avoid the oral polio, oral typhoid, BCG and yellow fever vaccines.
It is possible to detect a genetic contribution to venous thrombosis in a significant proportion of patients. This has led to a huge expenditure in clinical time and health resource. However, the gains to be made from the uncritical investigation of the causes of venous thromboembolism are limited and the approach raises significant issues in relation to the appropriateness of this form of genetic testing. In contrast, there are some acquired prothrombotic states that should be identified because the risk of further thrombosis may be sufficient to influence therapy. These states include antiphospholipid syndrome, myeloproliferative disorders, and cancer.
BACKGROUND AND OBJECTIVES: Routine irradiation of cellular blood products is not presently recommended for patients with non-Hodgkin's lymphoma (NHL). MATERIALS AND METHODS: We report the case of a 72-year-old-man with Waldenstrom's macroglobulinaemia who developed transfusion-associated graft-versus-host disease (TA-GvHD) 13 days following a non-irradiated red cell transfusion. RESULTS: The patient had not previously received purine analogues and none of the donors was homozygous for a human leucocyte antigen (HLA) haplotype that was shared by the recipient. Therefore, his only apparent risk factor was lymphoplasmacytoid NHL. CONCLUSIONS: This case further strengthens the argument that NHL per se is a risk factor for TA-GvHD and supports the proposal that the guidelines for prophylactic irradiation of cellular blood products be extended to include all cases of NHL.
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In a formal study, we have identified increasing age, pretreatment renal impairment and diabetes mellitus as risk factors for the development of intravenous immunoglobulin-induced renal failure. Identification of these characteristics in potential recipients should alert clinicians to the associated increased risk of this serious complication.
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Conditions which result in hypercoagulable blood or venous stasis may predispose to the development of deep vein thrombosis (DVT). Most of the recently described risk factors for DVT induce a hypercoagulable state. Over a 3-year period we have observed anomaly of the inferior vena cava (IVC) in four young patients presenting with spontaneous unprovoked DVT. This is a greater than expected rate (5% observed versus 0.5% expected). Further, bilateral DVT, which constitutes less than 10% of cases in most series, was present in three of the four cases. Anomaly of the IVC is a rare example of a prevalent congenital condition that predisposes to DVT, presumably by favouring venous stasis. This diagnosis should be considered in young patients with spontaneous and bilateral DVT.
The role of oral Vitamin K administration in the reversal of anticoagulation is not yet clear because of a paucity of data on the early effects of treatment, apparent differences in efficacy between preparations and a lack of data comparing oral with intravenous administration. We have compared the effects on the International Normalized Ratio (INR) and activities of the Vitamin K-dependent clotting factors II, VII, IX and X at 4 h and 24 h after administration of three oral Vitamin K preparations and of intravenous Vitamin K in 64 anticoagulated patients who required non-urgent partial correction of anticoagulation. Our data confirm that correction of anticoagulation is more rapid after intravenous administration of Vitamin K than after oral administration of similar or larger doses. At 24 h, satisfactory correction of INR can be achieved using low-dose Vitamin K given by either the intravenous or oral route. Our data, and that from previous studies, suggest that there may be differences in efficacy between orally administered products. Administration of Vitamin K by either route was accompanied by changes in the activities of the Vitamin K-dependent clotting factors that reflected their respective biological half-lives. In the 24 h after treatment, the relationship between the INR and the individual Vitamin K-dependent clotting factors was similar to that described previously in stable anticoagulated patients. We conclude that the reversal of anticoagulation with warfarin is achieved more rapidly by intravenous administration of Vitamin K. Satisfactory, but slower, reversal of anticoagulation can be effected using oral Vitamin K, but there may be differences in efficacy between the products tested in our study.
A 72-year-old woman presented with multiple sites of soft tissue bleeding and a left ulnar neuropathy due to a compartment syndrome. There were also clinical signs of hypothyroidism. Factor VIII:C (FVIII) levels were 6% and a FVIII inhibitor with a titre of 9 Bethesda units was detected. She had biochemical evidence of hypothyroidism and high titres of antithyroid antibodies were detected. Two episodes of life- or limb-threatening haemorrhage were successfully treated with FEIBA. The inhibitor disappeared following 2 months of immunosuppression with oral cyclophosphamide and corticosteroids. She then developed autoimmune haemolytic anaemia, which responded to further immunosuppression with oral prednisolone. The association between acquired haemophilia and systemic autoimmune disorders such as systemic lupus erythematosis is well recognized, but our description of an association with organ-specific autoimmunity is more unusual.
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Accurate diagnosis of the cause of bleeding is a prerequisite for determination of the optimal therapeutic response. Clinicians are generally aware of the more prevalent hemorrhagic syndromes but some rare acquired conditions are also of importance. In many of these, inhibitors of coagulation factors or of platelet adhesion/aggregation cause bleeding. These inhibitors are generally, but not always, immunoglobulins. In this review, the less common inhibitors of coagulation and hemostasis, as well as some important but rare nutritional, iatrogenic and disease associated hemorrhagic disorders, are described.