Biomedical subjects
M Makris
Publications and source records attributed to M Makris.
Air flight-related thrombosis: reality or hype?
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An evaluation of screening tests for defects in the protein C pathway: commercial kits lack sensitivity and specificity.
A comparative evaluation of four commercial coagulation test kits for screening the protein C pathway kits was performed at two centres. The tests were Acticlot V-OUT (V-OUT), the PCA test (PCA), the GradiThrom PCP test (PCP) and ProC Global (ProC). Reference ranges were established in 40 normal subjects and, with the exception of V-OUT and ProC, significant differences were observed between males and females. Consequently, sex-specific normal cut-off values (fifth percentile) were used that led to greatly improved sensitivity when compared with the manufacturers' recommended cut-off values. Plasma from patients with factor V Leiden (n = 23), congenital protein S deficiency (n = 19), congenital protein C deficiency (n = 11), lupus anticoagulant (n = 17) and thrombophilia with no demonstrable protein C pathway defect (n = 20) were tested. All kits showed 100% sensitivity to factor V Leiden, but sensitivity was variable for protein C deficiency (27-73%), and poor for protein S deficiency (29-35%). The lupus anticoagulant affected all kits to some degree, with 29-35% giving values below the fifth percentile of normal, whereas all kits gave 1/20 unexpected abnormal results in the thrombophilia group, with the same sample accounting for the abnormal results in three of the four kits. Overall sensitivity and specificity, respectively, for defects in the protein C pathway were: V-OUT, 60 and 91%; PCA, 70 and 86%; PCP 75 and 94%; and ProC, 66 and 88%. We conclude that all four kits lack the sensitivity and specificity required for routine laboratory screening for defects in the protein C pathway and cannot replace assays for the individual proteins of this system.
Venous thrombosis following the use of intermediate purity FVIII concentrate to treat patients with von Willebrand's disease.
We describe four patients with von Willebrand's disease (VWD) who experienced venous thrombosis after treatment with an intermediate purity factor VIII (FVIII) concentrate (Haemate P3) was used to cover invasive or surgical procedures. Most patients had additional risk factors for venous thromboembolism (VTE) and it is difficult to be certain of the contribution of the concentrate to the VTE. In view of the recognised association between high factor VIII activity (FVIII:C) levels and VTE there is a physiological basis for this complication and it is important to consider this when administering FVIII containing concentrates to VWD patients.
Mutations in the factor XI gene.
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The management of coumarin-induced over-anticoagulation Annotation.
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A comparison of the efficacy and rate of response to oral and intravenous Vitamin K in reversal of over-anticoagulation with warfarin.
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.
Guidelines on the diagnosis, management and prevention of hepatitis in haemophilia.
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The management of von Willebrand's disease-associated gastrointestinal angiodysplasia.
There is a recognized association between von Willebrand's disease and gastrointestinal angiodysplasia. Most previous publications have been reports of the association itself and there is little published on the management and long-term follow-up of affected patients. We report our experience and follow-up of six patients, and review the previous literature.
Personal practice: An approach to investigation of easy bruising.
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Recent onset of bleeding and gross coagulopathy.
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Recent onset of bleeding and gross coagulopathy.
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Genetic analysis, phenotypic diagnosis, and risk of venous thrombosis in families with inherited deficiencies of protein S.
Protein S deficiency is a recognized risk factor for venous thrombosis. Of all the inherited thrombophilic conditions, it remains the most difficult to diagnose because of phenotypic variability, which can lead to inconclusive results. We have overcome this problem by studying a cohort of patients from a single center where the diagnosis was confirmed at the genetic level. Twenty-eight index patients with protein S deficiency and a PROS1 gene defect were studied, together with 109 first-degree relatives. To avoid selection bias, we confined analysis of total and free protein S levels and thrombotic risk to the patients' relatives. In this group of relatives, a low free protein S level was the most reliable predictor of a PROS1 gene defect (sensitivity 97.7%, specificity 100%). First-degree relatives with a PROS1 gene defect had a 5.0-fold higher risk of thrombosis (95% confidence interval, 1. 5-16.8) than those with a normal PROS1 gene and no other recognized thrombophilic defect. Although pregnancy/puerperium and immobility/trauma were important precipitating factors for thrombosis, almost half of the events were spontaneous. Relatives with splice-site or major structural defects in the PROS1 gene were more likely to have had a thrombotic event and had significantly lower total and free protein S levels than those relatives having missense mutations. We conclude that persons with PROS1 gene defects and protein S deficiency are at increased risk of thrombosis and that free protein S estimation offers the most reliable way of diagnosing the deficiency. (Blood. 2000;95:1935-1941)
Influence of the -675 4G/5G dimorphism of the plasminogen activator inhibitor 1 promoter on thrombotic risk in patients with factor V Leiden.
Elevated plasminogen activator inhibitor 1 (PAI-1) levels are associated with venous thromboembolism, although their significance is unclear. PAI-1 levels are influenced by a PAI-1 promoter dimorphism (4G/5G), the 4G allele being associated with increased PAI-1 activity. We investigated whether the 4G allele influenced thrombotic risk by studying 99 symptomatic factor V (FV) Leiden heterozygotes and 99 healthy subjects. The 4G allele was more prevalent among cases than among healthy subjects (chi2 = 8.00, P = 0.005) and the odds ratio (OR) for thrombosis associated with either heterozygosity or homozygosity for the 4G allele was 2.43 (P = 0. 011). We conclude that carriership of the 4G allele was more prevalent in patients who already carried factor V Leiden than in control subjects without factor V Leiden.
Monthly haemoptysis in a woman with platelet storage pool disease.
A 26-year-old female with known platelet storage pool disease presented with a short history of recurrent haemoptysis. Initial investigations were unhelpful until the cyclical nature of the symptoms became apparent prompting the unusual diagnosis of pulmonary endometriosis to be made. This was subsequently confirmed on premenstrual CT scanning. The introduction of a specific hormonal therapy and multidisciplinary input was ultimately successful.
Hyperhomocysteinemia and thrombosis.
It has been known for some time that patients with homocystinuria are at an increased risk for both venous and arterial thrombosis. More recently it has been found that even moderate increases in homocysteine levels are associated with increased risk for deep venous thrombosis, myocardial infarction, cerebral infarction and peripheral vascular disease. It is possible, with the use of folic acid, vitamin B12 and vitamin B6, to correct the elevated homocysteine levels but it has not yet been demonstrated that by doing so the natural history of the disorder is altered.
Evaluation of a global screening assay for the investigation of the protein C anticoagulant pathway.
We have evaluated a global screening test for the protein C pathway, the 'ProC Global' (Dade Behring Ltd, Milton Keynes, UK). Patient groups tested included inherited protein C or S deficient and inherited/acquired activated protein C resistance. Results showed that protein C deficiencies and activated protein C resistance could be successfully detected with this test whereas deficiencies of protein S were less readily distinguished from the normal population. The ProC Global was unreliable in patients with antiphospholipid antibodies, raised plasma factor VIII:C and in those receiving oral anticoagulant therapy.
Poor reversal of low molecular weight heparin by protamine.
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