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Biomedical subjects

M Makris

Publications and source records attributed to M Makris.

At least 19 recordsLinked to original sources
PubMed2007

Haemoperitoneum associated with ovulation in women with bleeding disorders: the case for conservative management and the role of the contraceptive pill.

Haemoperitoneum secondary to ruptured corpus luteum is a rare complication for women on anticoagulants and with certain congenital bleeding disorders. A surgical approach is often taken, leading to oophorectomy in many cases. We describe three patients presenting with haemoperitoneum in association with factor VII deficiency, factor X deficiency and sitosterolaemia. In two of the patients, recurrent episodes occurred prior to introduction of the oral contraceptive pill. Conservative management with blood product and factor concentrate support was successful in avoiding surgery in three of the five episodes of bleeding. These cases demonstrate that preservation of ovarian function is possible with a conservative approach and recurrent episodes may be prevented by suppression of ovulation.

Adult↗
PubMed2006

Treatment of chronic hepatitis C in patients with haemophilia: a review of the literature.

Chronic hepatitis C is a major cause of morbidity and mortality in haemophilia patients. In contrast to studies in the general population, the studies of antiviral therapy in haemophilia patients are limited and often include small numbers of patients. A review of the literature was performed to assess the efficacy of interferon (IFN)-based therapy for patients with haemophilia chronically infected with hepatitis C virus (HCV). Studies were identified by electronic searches (Medline, Embase) and hand searches in references of key articles. Data of the included studies were pooled, and responses to therapy were stratified according to treatment regimen, HIV co-infection status, and treatment history. The main outcome was a sustained virological response (SVR) defined as absence of HCV RNA both at the end of treatment and 24-week post-treatment. Thirty-five studies were identified that included 1151 patients. After pooling the data of included patients, the SVR in HIV-negative treatment naïve patients was 22% for IFN monotherapy, 43% for IFN and ribavirin, and 57% for pegylated IFN and ribavirin, respectively. Re-treatment with IFN and ribavirin of those who failed to respond to previous IFN monotherapy was successful in 33%. In HCV/HIV-coinfected patients, response to IFN monotherapy was 8% and to IFN combined with ribavirin 39%. Responses to IFN-based therapy in patients with haemophilia have been improved over time and are nowadays approximately 50-60%. However, data on haemophilic HCV/HIV-coinfected patients and in patients who failed to respond to previous therapy are limited and future studies in these specific patient population are necessary.

Antiviral Agents↗
PubMed2005

Stomatocytic haemolysis and macrothrombocytopenia (Mediterranean stomatocytosis/macrothrombocytopenia) is the haematological presentation of phytosterolaemia.

Phytosterolaemia (sitosterolaemia) is a recessively inherited metabolic condition in which the absorption of both cholesterol and plant-derived cholesterol-like molecules at the gut is unselective and unrestricted. In haematology, Mediterranean stomatocytosis or Mediterranean macrothrombocytopenia is a poorly understood haematological condition that combines stomatocytic haemolysis with the presence of very large platelets. Five pedigrees showing this haematology were identified. Gas chromatography mass spectrometry (GC-MS) showed that all of the patients with this highly specific haematology had grossly elevated levels of phytosterols in the blood, diagnostic of phytosterolaemia. All showed mutations in the ABCG5 and ABCG8 previously linked to phytosterolaemia. Three pedigrees showed five new mutations, while two pedigrees showed the common W361X mutation in ABCG8. We draw the following four conclusions: (i) that Mediterranean stomatocytosis/macrothrombocytopenia is caused by an excess of phytosterols in the blood; (ii) that phytosterolaemia, which does not respond to standard statin treatment, can be diagnosed via the distinctive haematology described here, even when the cholesterol is normal; (iii) that phytosterolaemia should be considered in the differential diagnosis of all patients with large platelets; and (iv) that the platelet size should be noted in patients with hypercholesterolaemia.

ATP Binding Cassette Transporter, Subfamily G, Mem↗
PubMed2005

Risk of a first venous thrombotic event in carriers of a familial thrombophilic defect. The European Prospective Cohort on Thrombophilia (EPCOT).

BACKGROUND: Reliable risk estimates for venous thrombosis in families with inherited thrombophilia are scarce but necessary for determining optimal screening and treatment policies. OBJECTIVES: In the present analysis, we determined the risk of a first venous thrombotic event in carriers of a thrombophilic defect (i.e. antithrombin-, protein C- or protein S deficiency, or factor V Leiden). PATIENTS AND METHODS: The asymptomatic carriers had been tested prior to this study in nine European thrombosis centers because of a symptomatic carrier in the family, and were followed prospectively for 5.7 years on average between March 1994 and January 2001. Annually, data were recorded on the occurrence of risk situations for venous thrombosis and events (e.g. venous thrombosis, death). RESULTS: Twenty-six of the 575 asymptomatic carriers (4.5%) and seven of the 1118 controls (0.6%) experienced a first deep venous thrombosis or pulmonary embolism during follow-up. Of these events, 58% occurred spontaneously in the carriers compared with 43% in the controls. The incidence of first events was 0.8% per year (95% CI 0.5-1.2) in the carriers compared with 0.1% per year (95% CI 0.0-0.2) in the controls. The highest incidence was associated with antithrombin deficiency or combined defects, and the lowest incidence with factor V Leiden. CONCLUSIONS: The incidence of venous events in asymptomatic individuals from thrombophilic families does not exceed the risk of bleeding associated with long-term anticoagulant treatment in the literature (1-3%).

Adolescent↗
PubMed2004

Recombinant Factor VIIa concentrate versus plasma derived concentrates for the treatment of acute bleeding episodes in people with Haemophilia A and inhibitors.

BACKGROUND: In some people with haemophilia, therapeutic clotting agents are recognised as a foreign protein and anti-FVIII antibodies, known as 'inhibitors', are produced. This review investigates which treatment most effectively arrests acute bleeding in people with haemophilia A and inhibitors. OBJECTIVES: To determine the clinical effectiveness of recombinant FVIIa concentrate in comparison to plasma-derived concentrates for the treatment of acute bleeding episodes in people with haemophilia A and inhibitors. SEARCH STRATEGY: We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group trials register which comprises of references identified from comprehensive electronic database searches and handsearching of relevant journals and abstract books of conference proceedings. Date of the most recent search of the Group's trials register: September 2003. SELECTION CRITERIA: Randomised (RCTs) and quasi-randomised controlled clinical trials comparing Recombinant FVIIa concentrate to human plasma-derived concentrates (high-dose human or recombinant FVIII concentrate; prothrombin complex concentrates (PCCs); activated prothrombin complex concentrate (aPCC)) in people with haemophilia A. Comparisons with animal derived products were excluded. DATA COLLECTION AND ANALYSIS: No studies were found that were eligible for inclusion in this review. MAIN RESULTS: A total of four studies were identified by the searches, however, none of these were eligible for inclusion in this review. REVIEWERS' CONCLUSIONS: No RCTs on the relative effectiveness of Recombinant FVIIa concentrate compared to human plasma-derived concentrates in people with haemophilia A and inhibitors were identified for inclusion in this review. The research evidence on which to base clinical decisions is therefore limited to case reports, and other less robust evidence. There is need for a well-designed, adequately-powered randomised controlled trial to assess the relative benefits and risks of using Recombinant FVIIa concentrate compared to human plasma-derived concentrates in people with haemophilia A and inhibitors.

Acute Disease↗
PubMed2004

SSC/ISTH classification of hemophilia A: can hemophilia center laboratories achieve the new criteria?

To assess the practicality of the recent Scientific and Standardization committee (SSC) of the International Society on Thrombosis and Haemostasis (ISTH) recommendations in respect of the classification of hemophilia we distributed samples from three untreated subjects with hemophilia A to 91 UK hemophilia centers (HCs), comprising 20 comprehensive care centers (CCCs) and 71 HCs. Laboratories were requested to perform their routine factor (F)VIII:C assays and to classify the severity of hemophilia. Median values of < 1 U dL-1 were obtained on two samples. However, for each of the two, approximately 30% of laboratories obtained results in the range 1-29 U dL-1 and 1-33 U dL-1 respectively. For one of these samples 17 laboratories diagnosed severe hemophilia despite obtaining FVIII:C levels in the range 1-5 U dL-1. The median FVIII:C for the third sample was 5.8 U dL-1 with a range of 1.5-36 U dL-1. For this sample eight centers diagnosed severe hemophilia. Fifty-four laboratories obtained a result > 5 U dL-1; 21 of these diagnosed mild hemophilia, 31 moderate hemophilia and two severe hemophilia. Results from CCCs were more accurate and more precise than those from HCs. Our results indicate a need for improved standardization of FVIII assays. In the UK there remains a lack of consensus in respect of the laboratory diagnostic criteria for the classification of hemophilia A.

Clinical Laboratory Techniques↗
PubMed2004

Unconventional diagnosis of Normandy-type von Willebrand's disease in a blood donor.

We report the case of a long-standing female blood donor whose blood donation was processed for cryoprecipitate. The cryoprecipitate unit was chosen at random for FVIII:C estimation as part of the quality control, and a low FVIII:C level was identified. The cause of this was subsequently shown to be the Normandy variant of type-2 von Willebrand's disease due to a homozygous Arg854Gln mutation in the von Willebrand factor gene.

Blood Component Transfusion↗
PubMed2004

Hereditary thrombophilia and fetal loss: a prospective follow-up study.

BACKGROUND: As the placental vessels are dependent on the normal balance of procoagulant and anticoagulant mechanisms, inherited thrombophilia may be associated with fetal loss. OBJECTIVES: We performed a prospective study to investigate the relation between inherited thrombophilia and fetal loss, and the influence of thromboprophylaxis on pregnancy outcome. PATIENTS AND METHODS: Women were enrolled in the European Prospective Cohort on Thrombophilia (EPCOT). These included women with factor (F)V Leiden or a deficiency of antithrombin, protein C or protein S. Controls were partners or acquaintances of thrombophilic individuals. A total of 191 women (131 with thrombophilia, 60 controls) had a pregnancy outcome during prospective follow-up. Risk of fetal loss and effect of thromboprophylaxis were estimated by frequency calculation and Cox regression modelling. RESULTS: The risk of fetal loss appeared slightly increased in women with thrombophilia without a previous history of fetal loss who did not use any anticoagulants during pregnancy (7/39 vs. 7/51; relative risk 1.4; 95% confidence interval 0.4, 4.7). Per type of defect the relative risk varied only minimally from 1.4 for FV Leiden to 1.6 for antithrombin deficiency compared with control women. Prophylactic anticoagulant treatment during pregnancy in 83 women with thrombophilia differed greatly in type, dose and duration, precluding solid conclusions on the effect of thromboprophylaxis on fetal loss. No clear benefit of anticoagulant prophylaxis was apparent. CONCLUSIONS: Women with thrombophilia appear to have an increased risk of fetal loss, although the likelihood of a positive outcome is high in both women with thrombophilia and in controls.

Adolescent↗
PubMed2004

Familial thrombophilia and lifetime risk of venous thrombosis.

BACKGROUND: We started a large multicenter prospective follow-up study to provide reliable risk estimates of venous thrombosis in families with various thrombophilic defects. OBJECTIVES: This paper describes data collected at study entry on venous events experienced before study inclusion, i.e. the baseline data. PATIENTS/METHODS: All individuals (probands, relatives) registered in nine European thrombosis centers with the factor (F)V Leiden mutation, a deficiency of antithrombin, protein C or protein S, or a combination of these defects, were enrolled between March 1994 and September 1997. As control individuals, partners, friends or acquaintances of the thrombophilic participants were included. Incidence and relative risk of objectively confirmed venous thrombotic events (VTEs) prior to entry were calculated for the relatives with thrombophilia and the controls. RESULTS: Of the 846 relatives with thrombophilia (excluding probands), 139 (16%) had experienced a VTE with an incidence of 4.4 per 1000 person years. Of the controls, 15 of the 1212 (1%) controls had experienced a VTE with an incidence of 0.3 per 1000 person years. The risk of venous thrombosis associated with familial thrombophilia was 15.7 (95% CI 9.2-26.8) and remained similar after adjustment for regional and sex-effects (16.4; 95% CI 9.6-28.0). The highest incidence per 1000 person years was found in relatives with combined defects (8.4; 95% CI 5.6-12.2), and the lowest incidence was found in those with the FV Leiden mutation (1.5; 95% CI 0.8-2.6). CONCLUSIONS: Considerable differences in the lifetime risk of VTE were observed among individuals with different thrombophilia defects.

Adolescent↗
PubMed2003

Immunization of patients with bleeding disorders.

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.

Adolescent↗