[Prevalence of Elevated Lipoprotein (a) Levels in Patients < 60 Years of Age with Retinal Vein Occlusion]. / Prävalenz erhöhter Lipoprotein(a)-Spiegel bei unter 60-jährigen Patienten mit venösen retinalen Gefäßverschlüssen.

BACKGROUND: The potential impact of elevated Lipoprotein (a) [Lp(a)] levels on retinal venous occlusive (RVO) diseases with regard to age and various risk factors has not been studied extensively. PATIENTS AND METHODS: In a retrospective case-control study, thrombophilia data of 106 young patients (< 60 years at the time of the RVO or a previous thromboembolic event) with RVO and 76 healthy subjects were evaluated. RESULTS: Elevated Lp(a) plasma levels were significantly more prevalent among RVO patients (29.2 %) than among controls (9.2 %; p = 0.0009). Lp(a) levels were found to be significantly (p = 0.012) different between patients and controls. Moreover, we found that an unusual personal or family history of thromboembolism was a strong predictor of elevated Lp(a) (p = 0.03). We observed a significant correlation between elevated Lp(a) and other coagulation disorders (p = 0.005). Multivariate analysis showed that elevated lipoprotein(a) levels (OR: 3.5; p = 0.003) were an independent risk factor for the development of RVO. CONCLUSIONS: Elevated plasma levels of Lp(a) are associated with the development of RVO. Selective screening of young patients and subjects with a personal or family history of thromboembolism may be helpful in identifying RVO patients with elevated Lp(a).

Haemophilia patients' unmet needs and their expectations of the new extended half-life factor concentrates.

INTRODUCTION: National Member Organisations (NMO) of persons with haemophilia (PWH) from the DACH Region (D = Germany, A = Austria, CH = Switzerland) were interested to better understand PWH's expectations and concerns of extended half-life (EHL) factor concentrates (FC) before availability in these countries. METHODS: Based on an expert meeting and focus groups conducted across Germany a survey for haemophilia patients and their parents was developed and was sent out to 2,644 PWH. RESULTS: One thousand and seven questionnaires were sent back (38.1%); 743 adults and 262 parents. Most patients had haemophilia A (84.5%), were severely affected (73.7%), received prophylaxis (57%) and used recombinant FC (60.2%). One-quarter did not know the correct half-life of their FC [HA/FVIII: 26%, HB/FIX: 31.1%]. Four percent were unsatisfied with their current FC, mainly with short half-life of FC and difficult manageability. They expected from new EHL products less frequent injections (55.2%), better efficacy (32.1%) and safety/no side effects (15.7%); 59.5% would be willing to switch to new products if they have a prolonged half-life and the same safety of the current FC. They wish more information about half-life (84.4%), possible side-effects (81.3%) and efficacy (77%) and wanted to receive information about new products from their haemophilia treater (76.3%) and the newsletter of their NMO (74.3%). Significant differences across countries were found. CONCLUSIONS: The representative survey could show that although PWH were generally satisfied with their current FC, the majority would be willing to switch to EHL products assuming half-life is prolonged and has the same safety of the current FC.

Co-morbidities and bleeding in elderly patients with haemophilia-A survey of the German, Austrian and Swiss Society of Thrombosis and Haemostasis Research (GTH).

BACKGROUND: Nowadays patients with haemophilia survive longer due to improvements in haemophilia care. It has been hypothesized that the bleeding type and frequency may vary with age and are influenced by co-morbidities and co-medication in elderly patients. OBJECTIVES: To investigate a large group of patients older than 60 years of age with haemophilia concerning haemophilia treatment, bleeding pattern changes, co-morbidities, co-medication, bleeding sites and patient mortality. METHODS: A retrospective multi-centre data collection study was initiated on behalf of the German, Austrian and Swiss Society of Thrombosis and Haemostasis Research (GTH). Parameters of interest were investigated over the 5 years prior to study entry. RESULTS: A total of 185 haemophilia patients (mean age, 69.0±7.0 years, 29% with severe haemophilia) were included in the study. Regular prophylaxis was performed in 30% of the patients with severe haemophilia. In total, the annual bleeding rate was 2.49 and in patients with severe haemophilia 5.61, mostly caused by joint bleeds. Hypertension was the most common co-morbidity, but it occurred significantly less frequently than in an age-matched general population older than 70 years; 12% of the patients suffered from ischaemic heart disease, and 13% of the patients received anticoagulant or antiplatelet therapy. Within the observation period, 17% of the patients with severe haemophilia developed a higher frequency of bleeding symptoms, which was significantly associated with the use of antiplatelet or anticoagulant drugs. CONCLUSIONS: The most common co-morbidity of the patient population was hypertension, a considerable part had ischemic heart disease and antiplatelet or anticoagulant drugs.

Adherence to prophylactic treatment in patients with haemophilia in Germany.

INTRODUCTION: Adherence to prophylactic treatment in haemophilia is important for patient outcome. AIM: This study analysed the influence of potential impact factors on adherence assessed through the application of the German translation of the VERITAS-Pro questionnaire. METHODS: All members of the German haemophilia patient organisation (DHG) who suffer from severe or moderate haemophilia and are on continuous prophylactic treatment were asked to complete the VERITAS-Pro questionnaire. Further questions were added regarding the patients' age, severity of haemophilia, type A or B, frequency of prophylaxis, pain level, factor application self or non-self and co-morbidities. RESULTS: Responses of 397 patients on continuous prophylactic treatment, 0-80 years old, were analysed according to several age groups: 0-14, 15-19, 20-59 (20-29 and 30-39) and ≥60 years of age. The mean total VERITAS-Pro score for the whole sample was 36.7 ± 11.7 (range of 24-86). The scores were significantly higher, indicating the poorest adherence, in patients between 20 and 59 years of age (41.1 ± 11.7) compared with the other age groups (30.0-35.7). Adherence to treatment was highest in patients between 0 and 14 years of age in all subscales of the VERITAS-Pro. The following potential risk factors for non-adherence were evaluated in all age groups: organisation suffering (care by a haemophilia centre), severity and type of haemophilia, factor concentrate administration and the presence of co-morbidities. CONCLUSION: The identification of significant differences between age groups in special subscales of adherence and impact factors offers tailored starting points for improvements of adherence to prophylactic treatment.

Prospective evaluation of treatment regimens, efficacy and safety of a recombinant factor VIII concentrate in haemophilia A: the German EffeKt study.

INTRODUCTION: Collecting clinical data under routine conditions remains important to monitor continuously efficacy and tolerability of an established product. AIM: This prospective observational study aimed at evaluating efficacy and tolerability of full-length sucrose-formulated recombinant FVIII (rFVIII-FS; KOGENATE(®) Bayer/KOGENATE(®) FS) in routine use and analysing concomitant diseases and medication. METHODS: Haemophilia A patients treated with rFVIII-FS were followed up for 24 or 36 months. Efficacy, tolerability, concomitant medication and diseases were assessed at yearly intervals. RESULTS: Two hundred and twenty-one documented patients were mainly pretreated, predominantly with prophylaxis (74%). On study, 54 (31%) patients in the efficacy set (n = 174) documented regular prophylaxis, 91 patients (52.3%) failed to document their prescribed prophylactic infusions, 25 (14.4%) received on-demand treatment and four patients (2%) inhibitor adapted therapy. Patients on regular prophylaxis reported 8.4% of infusions for bleeding treatment and on-demand patients reported 55.3%. Young patients experienced mainly trauma-related bleedings and older patients reported spontaneous bleedings. Joint status was good overall. Median annual spontaneous joint bleeding rate in all groups was zero. A total of 79.0% of all bleedings were successfully treated with one or two infusions. Degenerative arthropathy and arterial hypertension were the most prominent concomitant diseases. Eighty-seven patients (40.5%) took at least one concomitant drug on study, mostly drugs for pain treatment related to haemophilic arthropathy. Two patients presented with positive inhibitor titres on study, one of them was a previously untreated patient and the other had a positive inhibitor history. CONCLUSION: This study corroborates the tolerability and efficacy profile of rFVIII-FS.

von Willebrand's disease: a report from a meeting in the Åland islands.

von Willebrand's disease (VWD) is probably the most common bleeding disorder, with some studies indicating that up to 1% of the population may have the condition. Over recent years interest in VWD has fallen compared to that of haemophilia, partly the result of focus on blood-borne diseases such as HIV and hepatitis. Now the time has come to revisit VWD, and in view of this some 60 international physicians with clinical and scientific interest in VWD met over 4 days in 2010 in the Åland islands to discuss state-of-the-art issues in the disease. The Åland islands are where Erik von Willebrand had first observed a bleeding disorder in a number of members of a family from Föglö, and 2010 was also the 140th anniversary of his birth. This report summarizes the main papers presented at the symposium; topics ranged from genetics and biochemistry through to classification of VWD, pharmacokinetics and laboratory assays used in the diagnosis of the disease, inhibitors, treatment guidelines in different age groups including the elderly who often have comorbid conditions that present challenges, and prophylaxis. Other topics included managing surgeries in patients with VWD and the role of FVIII in VWF replacement, a controversial subject.

Vitamin D: an instrumental factor in the anti-phospholipid syndrome by inhibition of tissue factor expression.

BACKGROUND AND AIMS: Antiphospholipid syndrome (APS) is a systemic autoimmune disease characterised by thrombosis, obstetric complications and the presence of anti-phospholipid antibodies such as anti-ß2GPI-Abs. These antibodies may set off the coagulation cascade via several mechanisms, including the induction of tissue factor (TF) expression. Vitamin D has recently emerged as an immunomodulator that might exert an anti-thrombotic effect. Therefore, we studied serum vitamin D levels in a cohort of APS patients, as well as the effect of vitamin D in an in vitro model of APS-mediated thrombosis. METHODS: Serum vitamin D levels were measured in 179 European APS patients and 141 healthy controls using the LIAISON chemiluminescent immunoassay, and the levels were evaluated in conjunction with a wide spectrum of clinical manifestations. In an vitro model, anti-ß2GPI antibodies were purified from four patients with APS to evaluate the expression of TF in activated starved human umbilical vein endothelial cells. The effect of vitamin D (1,25-dihydroxyvitamin D, 10 nm) on anti-ß2GPI-Abs mediated TF expression was analysed by immunoblot. RESULTS: Vitamin D deficiency (serum level ≤15 ng/ml) was documented in 49.5% of our APS patients versus 30% of controls (p<0.001) and was significantly correlated with thrombosis (58% vs 42%; p<0.05), neurological and ophthalmic manifestations, pulmonary hypertension, livedo reticularis and skin ulcerations. In vitro vitamin D inhibited the expression of TF induced by anti-ß2GPI-antibodies. CONCLUSIONS: Vitamin D deficiency is common among APS patients and is associated with clinically defined thrombotic events. Vitamin D inhibits anti-ß2GPI-mediated TF expression in vitro. Thus, vitamin D deficiency might be associated with decreased inhibition of TF expression and increased coagulation in APS. Evaluation of vitamin D status and vitamin D supplementation in APS patients should be considered.

Does haemophilia influence cancer-related mortality in HIV-negative patients?

Clinical investigations and animal studies suggest haemophilia specific effects on cancer-related mortality aside from virus induced malignancies. Analysis of results in the literature proposes that coagulation factor deficiency might inhibit cancer metastasis through decreased activation of thrombin. On the other hand, substitution of coagulation factor might increase cancer rates. A review of epidemiological studies was conducted to survey the clinical data on cancer rates. Clinical investigations concerning cancer-related mortality in haemophilia always deal with virus-related malignancies caused by HIV and/or hepatitis C virus (HCV) infections. Therefore, analysis of cancer rates and standardized mortality ratios (SMR) of cancer in the literature was conducted under exclusion of HIV infection and concomitant malignancies like non-Hodgkin-lymphomas and under exclusion of HCV-related deaths caused by liver disease and hepatocellular carcinoma. The survey covers epidemiological studies which report causes of deaths of more than 8000 haemophilia patients, including more than 2700 HIV-negative patients. Results show virus independent cancer rates of 8-16% of deaths. Analysis of corresponding SMRs supports the hypothesis that cancer rates, unaffected through HIV or hepatoma, are decreased in haemophilia when compared with the general population. Prospective data collection regarding factor consumption as well as severity of haemophilia in virus negative cancer patients is needed to investigate the interaction between haemophilia and cancer.

Association between phenotype and genotype in carriers of haemophilia A.

Female carriers of haemophilia might suffer from increased bleeding tendency therefore the assessment of the bleeding risk is very important for improving care. This single-centre study documents the occurrence of bleedings in 46 carriers of haemophilia A including bleeding after tooth extraction (77%), easy bruising (67%), postsurgical bleeding (61%), menorrhagia (50%) or prolonged postpartum bleeding (43%). The F8 gene mutation of all 46 carriers (median age: 36.5 years, 15-80 years; mean FVIII:C activity: 59 ± 24.45%; normal range: 64-167%) was determined, and family history of haemophilia was recorded. For analysis, the bleeding tendency of the carriers was differentiated by severity into three groups. There was no statistically significant difference of FVIII:C between these groups. However, a correlation was found between the severity of bleeding tendency and the type of F8 gene mutation (P < 0.05) as well as the severity of haemophilia in affected male relatives (P < 0.0005). Results show that even carriers with a FVIII:C activity as high as 50-60% are at increased risk of bleeding. Incidence and intensity of bleeding symptoms of haemophilia A carriers are high and correlated with the phenotype of the male haemophilic relative and the underlying F8 gene mutation.

Patients with isolated prolonged in vitro bleeding time. Clinical symptoms.

UNLABELLED: In patients with isolated prolonged in vitro bleeding time there is no standardised treatment concept. With this study we characterized the extent of bleeding symptoms. PATIENTS, METHODS: All diagnoses known to cause prolonged in vitro bleeding time (PFA-100) (epinephrine-cartridge >160 s, ADP-cartridge > 120 s) have been excluded, such as platelet function disorders, effects of medications, nutrition or von Willebrand disease. 75 patients (77%, n = 58 women; 23%, n = 17 men, median age 46 (16-81) years were included. All bleeding symptoms have been stored in a databank with help of a comprehensive questionnaire. RESULTS: 78% (n = 54) of all patients reported of having had an operation, 69.8% (n = 37) of them described postoperative bleedings (p = 0.0373). 13.5% (n = 5) of the 54 could remember having been randomly treated by the administration of a transfusion and only 2.7% (n = 1) were treated by substitution of von Willebrand factor. 71% (n = 51) patients indicated haematoma (p = 0.8116). About 33.8% (n = 24) patients had gum bleeding and 40.8% (n = 29, p = 0.7808) patients reported bleeding after the dentist. 41.4% (n = 29) patients suffered under frequent epistaxis (p = 0.0212). There was no correlation between prolonged epinephrine bleeding time to VWF:Ag (rho = 0.16) nor to VWF:RCo (rho = 0.12) nor between prolonged epinephrine and ADP bleeding time (rho = 0.01) nor to ROTEM® analysis. CONCLUSION: Patients with isolated prolonged PFA are mainly women and can be affected by all kinds of bleedings while haematoma is the main symptom. VWD might not be causal.

[Does FVIII-activity increase with age in patients with haemophilia A and carriers of haemophilia A?]. / Hämophilie-A-Patienten und Konduktorinnen für Hämophilie A. Steigt die FVIII-Aktivität mit dem Lebensalter?

UNLABELLED: The retrospective cohort study surveys the influence of age, co-morbidity and laboratory values on FVIII-activity (FVIII:C) in patients with haemophilia A with (mild n = 48, moderate n = 10, severe n = 7 and carriers n = 23). Median observation was 19 years for patients with haemophilia A and 9,5 years for carriers. RESULTS: FVIII:C levels collected from patients with mild haemophilia A displayed a significant median increase of 6.5% with proceeding age (p = 0.0013). Patients with moderate haemophilia A (and carriers of haemophilia A) showed a non significant median increase of 1.05% (carriers 8%). Eight patients showed FVIII:C levels at last blood withdrawal that indicated a change of severity from moderate to mild haemophilia A. A significant correlation was found between FVIII:C and VWF:RCo (p = 0.0203) and AFP (p < 0.0005). The correlation between FVIII:C and triglycerides and LDH was significant negative (p < 0.0005). No significant correlation could be found for FVIII:C and co-morbidity, fibrinogen, cholesterol and VWF:Ag.

[Role of thrombelastometry for the monitoring of factor XIII. A prospective observational study in neurosurgical patients]. / Stellenwert der Thrombelastometrie für das Monitoring von Faktor XIII. Prospektive Observationsstudie bei neurochirurgischen Patienten.

UNLABELLED: Recently published studies give evidence, that an increased maximum lysis in the APTEM® - test (ML60 > 12%) of the ROTEM® (Tem International GmbH, Munich, Germany) might indicate a factor XIII deficiency (FXIII < 70%). It was the aim of this study to investigate the feasibility of thrombelastometric measurements with the ROTEM device to reflect the isolated influence of FXIII on clot stability and therefore to indicate potential factor XIII deficiencies. PATIENTS, METHOD: After approval by the local Scientific and Ethic Review Board, 26 consecutive patients, scheduled for elective craniotomy for tumour resection, were prospectively enrolled into this study. Blood samples were taken for conventional laboratory coagulation analyses, FXIII analyses and thrombelastometric measurements (EXTEM, FIBTEM and APTEM tests) after induction of general anaesthesia (T1), before skin incision (T2) as well as at (T3) and 24 hours after (T4) postoperative admission to ICU, respectively. Statistical analyses included Spearman rank order correlations and multiple linear regressions. RESULTS: FXIII concentrations did not correlate with the ML60 in the APTEM test at any measuring point. Neither platelet count nor fibrinogen nor FXIII concentrations were of predictive value for ML60 of the APTEM test. CONCLUSION: The results lead to the assumption that thrombelastometric measurements may not be appropriate for the perioperative monitoring of FXIII concentration.

Prolactin's role in the pathogenesis of the antiphospholipid syndrome.

Increased levels of serum prolactin have been reported in patients with various autoimmune diseases and have been associated with lupus disease activity. Currently, there is a lack of data regarding hyperprolactinaemia in patients with the antiphospholipid syndrome. Hence, this study was carried out in order to evaluate the prevalence and clinical significance of hyperprolactinaemia in antiphospholipid syndrome. A total of 172 European patients with antiphospholipid syndrome and 100 geographically and sex-matched healthy controls were included in the study; none had obvious causes of hyperprolactinaemia. All patients underwent clinical assessment for disease manifestations, in addition to laboratory assessment for serum prolactin, antiphospholipid antibodies and some other biomarkers of autoimmune diseases. The tests were performed utilizing the LIAISON® Analyzer (DiaSorin, Sallugia Italy). Hyperprolactinaemia was detected in 21/172 patients with antiphospholipid syndrome and 0/100 controls (p < 0.001). This significant difference was present in both genders and was obvious even after subgrouping the patients into primary and secondary antiphospholipid syndrome. When clinical features were compared, hyperprolactinaemia was associated with reproductive failure, including early and late pregnancy loss (p < 0.05), as well as intrauterine growth retardation (p < 0.05). Hyperprolactinaemia was negatively related to arthralgias, venous thrombosis, pulmonary microthrombosis, pulmonary hypertension in both primary antiphospholipid syndrome and antiphospholipid syndrome secondary to other diseases, and to neurological manifestations in primary antiphospholipid syndrome (p<0.05). The data indirectly imply that prolactin may play a role in the pathogenesis of antiphospholipid syndrome, especially antiphospholipid syndrome-related reproductive failure.

[Total knee replacement in haemophilic arthropathy. A clinical and radiological evaluation of 30 patients]. / Kniegelenksendoprothetik bei hämophiler Arthropathie. Klinische und radiologische Verlaufskontrolle mit 30 Patienten.

UNLABELLED: Purpose of this retrospective study was to evaluate our own results after total knee replacement in patients with haemophilia. Patients, material, method: 30 patients with haemophilia who underwent total knee replacement between 1987 and 2005 were included. We used the clinical and radiological Knee Society Score. Furthermore, the Petterson and the Arnold and Hilgartner score were applied. RESULTS: The mean age at the time of surgery was 43.2 (27-66). At the time of follow-up examination the mean age was 51.6 (30-82) years. The mean follow-up was 7.1 (2-20) years. Preoperative, he mean Arnold and Hilgartner score was 4.17 (±0.59) and the mean Petterson-Score was 9±2.29. Compared to the preoperative deficiency in knee function (KSS-Score 88.17±33.58) an improvement with 166.67 (±22.73) points was seen. 1 patient showed an aseptic loosening after 11 years. DISCUSSION: Total knee replacement in patients with haemophilia improves knee function and quality of life. The results of our study represent results in earlier published studies. Compared to a non-haemophilic normal population the rate of perioperative complications was not increased.

Clinical assessment of efficacy and safety of DDAVP.

UNLABELLED: The efficacy of DDAVP (1-deamino-8-D-arginine-vasopressin, desmopressin) in mild haemophilia A and von Willebrand disease (VWD) has been established and the use of this well tolerated drug has become clinical routine. In case of increased fluid intake and based on very rarely occurring hyponatraemia, the indication of administration of DDAVP intravenously (i. v.) has to be performed diligently in elderly patients and in children below the age of five years. Aim, patients: Due to clinical practice we were interested in finding prospective parameter potentially correlating with adverse reactions of DDAVP and initiated this study. From 2007 to 2008, we included 49 patients suspicious to suffer from mild haemophilia A (n = 1) or VWD (n = 48) and investigated efficacy and safety of DDAVP after intravenous administration (mean: 0.29±0.032 μg/kg body weight). They underwent clinical and laboratory investigation and were questioned with regard to potential adverse reactions immediately and three days after administration of DDAVP. RESULTS, CONCLUSION: Most adverse reactions were mild and no serious adverse drug reactions were either observed or reported by the subjects. We identified significant changes of heart rate, blood pressure and leucocytes after conduct of the DDAVP test. The value of these findings has to be investigated in later prospective randomized studies. Further research on identification of prospective parameter is currently ongoing.

Age-dependent increase of FVIII:C in mild haemophilia A.

Variability of FVIII:C levels in healthy individuals and age-dependent increase are a known phenomenon. In haemophilia, increasing FVIII:C levels with age have not been described yet. In our study, we evaluated this issue retrospectively in a cohort older than 45 years of 29 patients with mild haemophilia and 14 patients with moderate or severe haemophilia at last visit at the haemophilia centre Frankfurt. The median duration of observation evaluated in this study was 17 years (range 5-28). Results show a significant correlation of increasing FVIII:C levels with age in mild haemophilia (P = 0.000041) and a non-significant tendency to a higher increase in higher age (P = 0.085652). The median difference of FVIII:C level between the first and last measurement was 8% of normal plasma concentration (range -3% to +35%). Median FVIII:C level increase of patients younger than 62 years was 7.5% (range -3 to 22), median increase in older patients was 12% (range 0-35). This tendency could not be correlated to decreased number of bleedings, but FVIII substitution dosage should be adapted to changing plasma levels at higher age to prevent overdosing or thrombotic risks. Possible causes and contributing factors for increasing FVIII:C levels are discussed. Statistical significance remains to be confirmed in larger prospective studies also including younger patients.

Comorbidities and bleeding pattern in elderly haemophilia A patients.

The increasing numbers of comorbidities related to higher age and their treatment constitute a challenge in the treatment of haemophiliacs. Comparing prevalences of morbidities in the elderly haemophilia A population (n = 29) and the general elderly population of Germany reveals some differences. HCV infections are more frequent in the elderly haemophilia population (69% vs. 0.6%). Prevalence of cancer was five times higher than in the age matched general population (28% vs. 5.2%). Cardiac diseases seem to be less frequent although the prevalences of cardiovascular risk factors like hypertension, diabetes, and body mass index (BMI) >25 do not differ in comparison to the general population. A reduction of bleeding symptoms or dosage of FVIII could not be observed. There is a tendency of increasing bleeding symptoms with increasing age of the patients due to more frequent spontaneous joint bleedings, malignancies or treatment with phenprocoumon or ASA. In consequence, FVIII dosage had to be increased in eight patients (28%). Our patient population at the age >60 years is very small and no statistical evidence can be shown, therefore appropriate treatment of elderly haemophiliacs needs further evaluation in multicentre studies with sufficient patient numbers.

Treatment of haemophilia in the elderly.

UNLABELLED: Treatment of elderly patients with haemophilia is an upcoming challenge in haemophilia care. We included patients with haemophilia A older than 60 years of age, who visited our haemophilia centre between 2006 and 2008. We conducted a retrospective study focussing on the patients' co-morbidities as well as changes in their bleeding patterns between 2003 and 2008. RESULTS: There is a tendency of increasing bleeding symptoms with increasing age of the patients due to more frequent spontaneous joint bleedings, malignancies or treatment with phenprocoumon or ASS. In consequence, FVIII dosage had to be increased for 8 patients (28%). Chronic hepatitis C, coronary heart disease and malignancies are the most frequent co-morbidities.

Recurrent deep vein thrombosis, ovarian carcinoma and antibodies to mitochondria M5 in a patient with asymptomatic primary "plus" antiphospholipid syndrome: an unusual combination.

An asymptomatic thirty-eight-year-old female developed recurrent DVT at the latter end of her first pregnancy and in the puerperium. Blood tests revealed a moderately elevated ANF (1:640) with a speckled pattern, hyperglobulinemia, and antibodies to thyroid tissues. Two months postpartum, following neurological disturbances she was found to have a patent foramen ovale and had developed paradoxical emboli to the brain causing multiple arterial occlusions. However, she also had cerebral venous occlusions as well as deep venous thromboses and pulmonary emboli, indicating a generalised prothrombotic state. Abdominal ultrasound examination revealed the presence of tumour which, on surgical removal, proved to be an ovarian carcinoma. The only antiphospholipid antibodies detectable were antibodies to mitochondria Type M5 in moderately elevated titres.