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To investigate the thrombotic tendency in patients with systemic lupus erythematosus (SLE) by evaluating congenital and acquired abnormalities with an increased risk of thrombosis.A total of 53 patients with SLE were included in the study. Fifty-three healthy controls paired by age and sex were assessed. Anticardiolipin antibodies (aCL), anti β2 glycoprotein (aβ2GP), lupus anticoagulant (LAC), protein C (PC), protein S (PS), antithrombin (AT), acquired activated protein C, and homocysteinemia were evaluated. Comparisons for categorical variables were analyzed by ChiThe patients were all female and had a mean age of 30.6 years (16/58). The healthy controls were all female and their mean age was 30.8 years (17/56). Five patients (9.4%) developed venous thrombosis during the 24 months of follow-up. The antiphospholipid antibodies were positive in 17 patients (32.1%) and negative in all healthy controls (P=0.01). PS deficiency was noted in 17 patients (32.1%) and in 5 controls (P=0.004). Hyperhomocysteinemia was noted in 16 patients (30.2%) versus 3 controls (5.6%) (P=0.002). Test for PC deficiency and acquired activated protein C showed no significant difference between the two groups. No AT deficiency was found in the patients. The study of clinical and biological correlations based on the presence and absence of thrombophilic parameters concluded to a significant association between Protein C deficit and thrombosis (P=0.02) and acquired activated protein C resistance and thrombosis (P=0.04). There was no significant association between the APL and thrombosis.Thrombophilic abnormalities were significantly more frequent in lupus patients than in healthy controls. Thrombotic events were significantly associated with PC deficit and acquired protein C resistance. There was no correlation between antiphospholipid antibodies and thrombosis.

Patients treated by vitamin K antagonists (VKA) represent 1% of the population in France. We report a case of atypical necrotic leg ulcers induced by VKA.A 84-year-old woman was referred to our dermatology department because of necrotic leg ulcers that developed for the past 5weeks, and appeared spontaneously after the introduction of a VKA, fluindione. The etiological assessment was non contributive, in particular the search for thrombophilic factors. The skin biopsy found an aspect compatible with pyoderma gangrenosum. The outcome was favorable after discontinuing the fluindione and the switch to apixaban. A complete healing was obtained in 5months.We report an original case of necrotic leg ulcers induced by VKA without deficit of protein C or S, with a pyoderma like histology. Reported cases of ulcers induced by VKA are uncommon and the physiopathology is not well known. The involvement of VKA should be evoked in case of necrotic leg ulcer without specific etiology found.

Venous thromboembolic disease is a multifactorial, frequently recurrent pathology, whose treatment is based on anticoagulation. As part of the etiological investigation, screening for an inherited thrombophilia is framed by French guidelines published in 2009. The aim of the study is to assess the contribution of inherited thrombophilias testing in common practice.This is a retrospective single-center observational study. Over a period of a year, all records of patients who were screened for a hereditary thrombophilia were analyzed. The conformity of the indication of hereditary thrombophilia workup in balance with the guidelines, its completeness and therapeutic impact were studied.Of the 494 records analyzed, 225 were related to venous thromboembolism. Among them, there were 162 pulmonary embolisms or deep vein thrombosis of the lower limbs. In this subgroup, 57 % of records complied with guidelines and 69 % were complete. Thirty-four thrombophilias were highlighted: 4 protein S deficiencies, 1 protein C deficiency, 4 combined deficiencies, 17 factor V Leiden mutations and 8 factor II G20210A mutations. For one patient, hereditary thrombophilia diagnosis had profoundly changed the curative therapeutic approach.Adherence to French guidelines remains limited. In clinical practice, diagnosis of hereditary thrombophilia has little impact on the curative therapeutic approach in venous thromboembolic disease.

Severe congenital protein C deficiency is a rare life-threatening coagulopathy. In the early hours of life, the neonate presents with extensive purpura fulminans and substantial skin necrosis contrasting with a preserved general state and a negative infectious exam. Disseminated intravascular coagulation sets in secondarily. Prenatal outset of thrombotic events is a rare situation that worsens the prognosis, especially protein C replacement in utero is not available. We report a case of a male newborn of consanguineous parents who were asymptomatic carriers of heterozygous protein C deficiency. This infant presented prenatal ventricular hemorrhage with hydrocephalus and rapidly extensive postnatal skin necrosis that was not regressive in spite of fresh frozen plasma administrated after 24h of life. Prenatal diagnosis, early recognition, and urgent therapy with protein C replacement and anticoagulant treatment are crucial to improve the prognosis, avoid further damage after delivery, and prevent the devastating consequences of severe protein C deficiency.

Venous thromboembolic disease is increasingly recognized as an important cause of morbidity and mortality in children. In the neonatal period, thrombotic accidents suggest constitutional abnormalities of homeostasis, including congenital protein C deficiency. We report on a clinical case that helps review all the diagnostic elements and discuss actions to be taken in the neonatal period.A newborn infant was admitted for transient neonatal respiratory distress. The physical examination revealed a facial dysmorphism and a bilateral lumbar contact. Abdominal Doppler ultrasounds showed a thrombosis of the vena cava inferior and of the left renal vein. Investigations searching for a thrombophilic state revealed severe congenital protein C deficiency. The maternal level of protein C at 50% argues in favor of a heterozygote deficit, the rate being normal in the father. Therapeutic management was based on low-molecular-weight heparin. The ultrasound check showed regression and then disappearance of thrombosis. Genetic counseling was planned.In cases of neonatal thrombosis, seeking a deficiency anticoagulant factor, in particular of protein C, is essential in the newborn and in both parents. Therapeutic management is not codified. An individualized approach is appropriate in this very rare clinical situation.

Thrombotic events occurring in the course of celiac disease are frequently reported in the literature. The localization is often unusual, mainly affecting the hepatic veins. To our knowledge, this is the first report of intracardiac thrombosis occurring in a patient with celiac disease. A 32-year-old patient with celiac disease adhered poorly to his gluten-free diet. He suffered an ischemic stroke revealing an intracardiac thrombus, which, on radiological imaging, simulated a multiple myxoma. Histological examination of the resected tumor enabled the correct diagnosis. Biological findings revealed severe protein C and S deficiency. The patient improved with anticoagulant therapy and gluten-free diet.

Cutaneous necrosis is a rare complication of vitamin K antagonist therapy. It presents as cutaneous hemorrhagic necrosis and usually occurs at the start of treatment. We describe an atypical case of recurrent skin necrosis after two years of treatment with fluindione.A 70-year old woman with a history of venous thromboembolism and obesity presented with a large haemorrhagic necrosis of the abdominal wall. She had been treated with fluindione for two years. Genetic protein C deficiency was discovered. Resumption of vitamin K antagonist therapy was followed by recurrence of skin necrosis despite concomitant administration of heparin. Treatment with vitamin K antagonists could not be continued.This observation is unusual due to the late onset of skin necrosis. The condition usually begins shortly after initiation of vitamin K antagonist therapy, generally between the third and the sixth day of treatment. It is due to a transient hypercoagulable state in patients with protein C deficiency or, in rare cases, protein S deficiency. This late-onset skin necrosis, occurring many years after initiation of anticoagulant therapy, may be explained by a sudden worsening of pre-existing protein C deficiency due to infectious and iatrogenic factors.

Thrombotic events may occur in celiac disease. In this study, we analyzed clinical features and risk factors for thrombosis in seven patients who had celiac disease and thrombosis.We retrospectively studied 87 patients with adult celiac disease and identified seven cases of thrombosis. We searched if risk factors for thrombosis were identified and tested retrospectively antiphospholipid antibodies on the serum.In our study, the global prevalence of thrombosis was 8 %, and 5.7 % for spontaneous thrombosis, with venous thrombosis (n=5) or arterial thrombosis (n=1) or both (n=2). The seven patients consisted in six women and one man with a mean age of 44.8 years at time of thrombosis. Thrombotic events occurred before the diagnosis of celiac disease in four cases. In three cases, venous thrombosis was in unusual sites: portal (n=2), splenic vein thrombosis (n=1). In six cases, we identified risk factors for thrombosis, which could be linked to celiac disease: hyperhomocysteinemia (n=1), protein C and S deficiency due to vitamin K deficiency (n=3) and antiphospholipid antibodies (n=2).Such risk factors for thrombosis should be identified in patients in adult celiac disease in order to correct them and add a thromboembolic prophylaxis.

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L-asparaginase is commonly used in the chemotherapy regimens for acute lymphoblastic leukaemia. Its use is associated with thrombotic complications in 1 to 14 % of the cases. The pathogenesis of this complication is still unclear. However, the decrease of antithrombin seems to play an important role. We report a case of a 17-year old man with a acute lymphoblastic leukaemia, who developed a cerebral sinovenous thrombosis due to an acquired deficiency of antithrombin and protein C and S following L-asparaginase chemotherapy. We discuss the use of prophylactic supplements of antithrombin and the value of screening of thrombophilia based on the recent medical literature.

Rare thrombophilic states are mostly associated with recurrent venous thrombosis or severe thrombosis such as neonatal purpura fulminans. We review here the various causes of rare thrombophilic states.Rare thrombophilic states associated with recurrent venous thrombosis include the following: antithrombin deficiencies, homozygous for protein C or protein S deficiency or compound heterozygous, double heterozygous for genetic thrombophilia and the rare thrombophilia due to auto-antibodies. Their frequency in patients with venous thromboembolism is below 2%.These uncommon thrombophilic states require a treatment in a specialized department.

The aim of this study is to evaluate the frequency of protein C deficiency in venous thromboembolism in black African patients of Benin. It is a descriptive study. Inclusion criteria were: acceptance- having a venous thromboembolism. No exlusion criteria was retained. Protein C deficiency was diagnosed by quantitative technic with a Minividas materiel in the blood. Protein C dosage has been done before antivitamin k therapy and a second dosage has been done if the first one demonstrated a low level of protein C. Acuired aetiology have been research. For the 54 patients of this study mean age was 52.7±14.1 and sex-ratio 1.08. The frequency of protein C deficiency was 9.3% in all patients and 12.5% in those with clinical thrombophily (p=1). No acquired deficit has been found.

Thrombophilia may be defined as an acquired or congenital abnormality of hemostasis predisposing to thrombosis. Some of the inherited abnormalities such as factor V Leiden mutation, factor II G20210A mutation as well as deficiencies in antithrombin, protein C and protein S, are already known to be risk factors for venous thromboembolism. This review focuses on the link between these abnormalities and arterial thrombosis. Routine screening for these disorders is not indicated in most cases of arterial complications, but could be useful in some sub-groups of patients, such as young patients, smokers, patients on oral contraception, or those with premature occlusion after revascularization procedures. Anticoagulation rather than antiplatelet therapy may be preferable for these patients.

Post traumatic renal artery thrombosis is rarely described in the literature. This pathology can result from stretch injury to inelastic intima of the renal artery, or by the direct flow to the abdomen causing compression injury to the renal artery against the vertebral column. However, the association of this pathology with hematologic diseases (in particular protein C deficit) was never described. We report an observation of a 28-year-old man with an uneventful history who was admitted to the intensive care unit for traumatic head injury associated with post traumatic renal artery thrombosis requiring nephrectomy. The etiologic investigation of this thrombo-embolic complication reveals a protein C deficit. Our patient was improved under treatment. This original observation confirms that post traumatic renal artery thrombosis can be associated with hematologic diseases (in particular protein C deficit).

We report a case of Budd-Chiari syndrome caused by protein C deficiency. The association of thrombosis of the the inferior vein cava of the hepatic vein resulted in the development of epidural varices and a central and peripheral neurological syndrome. These symptoms, which are atypical in this disease, resolved after surgical treatment of the Budd-Chiari syndrome (cavoatrial and mesocaval stenting).

Myocardial infarction with normal coronary artery is ussually inaugural, with electric and clinical characteristics similar to those with atheroma. The role of constitutional or acquired abnormalities of haemostasis has been more incriminated in the pathogenesis of myocardial infarction with normal coronary. The aim of our study was to research abnormalities of haemostasis in patients with myocardial infarction and angiographically absolutely normal coronary arteries.Thirty nine patients with myocardial infarction and normal coronary arteries where included in our study. They were 33 males and 6 females aged between 22 and 75 years (44 + 13 years), in whom the deficiency in protein C and S. antithrombin, activated protein C resistance and antiphospholipid antibodies were assessed.Concurrent abnormalities of haemostasis were found in 10 patients: Antiphospholipid antibodies, found in 5 patients constitute the most frequent abnormality. The other abnormalities were deficiency in protein C in two cases, deficiency in protein S 2 cases, deficiency in antithrombin in 2 ceses and activated protein C resistance in 3 cases .In our study. in face of the high prevalence of these abnormalities, it seems reasonable to research them, especially in young patients with myocardial infarction with normal coronary artery. This should have an impact on the management of these patients.

Variceal bleeding is frequently the initial presentation of a previously unknown cirrhosis. Portal hypertension and its complications without liver cirrhosis should raise the possibility of presinusoidal portal hypertension, and the diagnosis of hepatoportal sclerosis. These patients need to be investigated for coagulation disorders. A hypercoagulable state is often associated. Risks and benefits of anticoagulation should be further investigated in these patients.

Genetic risk factors became a frequent predisposing cause of venous thromboembolism (VTE) since the discovery of two mutations: factor V Leiden and G20210A mutation of prothrombin gene. One of these both mutations is associated with around 25% of VTE events. Interaction of genetic risk factors, such as interaction of FV Leiden or G20210A mutation of prothrombin with antithrombin, protein C or protein S deficiencies, as well as interaction with acquired risk factors, have demonstrated that venous thrombosis is a multifactorial disease. The search for thrombophilia must be done in VTE occurring before the age of 45, in case of recurrencies and in case of familial history of VTE.

Many coagulation disorders have been associated with cerebral venous thrombosis. These disorders may be primary like protein C and S deficiency, antithrombine III deficiency and activated protein C resistance. Antiphospholipid antibodies represent an acquired disorders of coagulation. A prothrombotic state induced by more common factor including oral contraceptive, pregnancy and puerperium increases the venous thrombosis risk.

Abnormalities of the protein C anticoagulant pathway i.e. protein C and protein S deficiencies and factor V Leiden-related activated protein C resistance are among the most frequent risk factors for thrombosis in the Caucasian population. Until now, their screening is based upon the use of individual assays for each component. However, normal results are found in more than 70% of the tested patients. So, there was a rational behind the development of global assays to evaluate the functionality of the protein C pathway, as this would rationalize the use of costly specific assays. Such global assays are based on the ability of endogenous activated protein C generated by activation of protein C by a snake venom extract to prolong a clotting time. Up to now, two assays are commercially available, the ProC Global assay (Dade Behring) and the Protein C Pathway Test (Gradipore). Both were found to be highly sensitive for the factor V Leiden and for protein C deficiency, as confirmed by different studies in patients with a history of venous thrombosis. However, sensitivity of both global assays for protein S deficiency was found to be only moderate and highly variable depending of the cut-off level used. So, these global assays can be validly used for the screening of the factor V Leiden-related APC resistance and for protein C deficiency, but protein S have to be measured in all the cases. The overall sensitivity of these assays for abnormalities of the protein C pathway was dramatically different, since 40% of the patients without any known abnormality have a decreased response to the ProC Global assay versus less than 13% for the Protein C Pathway Test. These characteristics suggest that the clinical usefulness of these two global assays might be different.

In laboratory screening in patients with clinical thrombophilia (early thromboembolism episode50 years, spontaneous thrombosis, recurrent thrombosis, unusual site of thrombosis, thrombotic family history or coumarin-induced skin necrosis complication), an isolated or combined inherited thrombophilia can be observed: antithrombin (0.5 to 4.9 per cent), protein C (1.4 to 8.6 per cent) and protein S (1.4 to 7.5 per cent) deficiencies or factor V Leiden (20 to 30 per cent). Special attention is mandatory in prescribing biological exploration because of the many physiological or pharmacological interferences which can modify the results. Identification of a genetic defect may induce specific management and individuals should receive counselling regarding the implications of this diagnosis. Further prospective studies should help to determine the thrombotic risk in symptomatic and non-symptomatic patients with inherited thrombophilia and the risk/benefit ratio of laboratory screening for hereditary thrombophilia and therapeutic intervention.

Thromboses represent a rare event in children and may be due to a deficiency of antithrombin.A 10-year-old boy developed thrombosis due to a congenital quantitative deficiency in antithrombin, confirmed by molecular biology. His father was diagnosed with the same deficiency. The child was first treated with heparin and is now on antivitamin K. He is well 26 months after diagnosis.When a young patient presents with a thrombotic event, a congenital deficiency in one of the inhibitors of coagulation, one of which is antithrombin, should be looked for and the condition treated as soon as possible.

Background. - Thromboses represent a rare event in children and may be due to a deficiency of antithrombin. Case report. - A 10-year-old boy developed thrombosis due to a congenital quantitative deficiency in antithrombin, confirmed by molecular biology. His father was diagnosed with the same deficiency. The child was first treated with heparin and is now on antivitamin K. He is well 26 months after diagnosis. Conclusion. - When a young patient presents with a thrombotic event, a congenital deficiency in one of the inhibitors of coagulation, one of which is antithrombin, should be looked for and the condition treated as soon as possible. (C) 1999 Elsevier, Paris.

Management of deep venous thromboembolism both in terms of diagnosis and therapeutic and prophylactic strategies has been greatly improved by advances in knowledge of the main acquired and intrinsic risk factors.This is by far the most frequent coagulation disorder predisposing to venous thromboembolism. Other intrinsic factors favoring thrombus formation (anti-thrombin II, protein C or protein S deficiencies) are much more uncommon. Laboratory tests in search for these anomalies are indicated essentially for patients who develop repeated episodes of venous thrombus formation.Excepting specific cases, anticoagulant prophylaxis is not indicated in any of these anomalies beyond the usual treatment of a first episode. Among the risk factors for acquired deep vein thromboembolism, only surgery and certain obstetrical indications have been investigated sufficiently to define validated prophylaxis strategies. For medical risks, the benefit of anticoagulant prophylaxis has been demonstrated in certain disease states such as cancer, antiphospholipid syndrome and the acute phase of myocardial infarction although no widely accepted strategy has yet been established.

Thromboembolic disease results from an hypercoagulable state and multifactorial causes may lead to hypercoagulability. Thrombogenic risk factors can be acquired and/or inherited. For each thrombophilic patient, the main clinical features retained are: the patient age, the familial history, the recurrence of thromboembolic events, an unusual site of thrombosis. Anti-phospholipid antibodies, which are considered as acquired thrombogenic risk factors, can be detected with coagulation tests and/or Elisa methods. The association of antiphospholipid antibodies with thrombosis is defined as the anti-phospholipid syndrome. Last decades, genetic risk factors were identified. First of all, antithrombin, protein C and protein S deficiencies were described. These deficiencies are involved in about 10% of patients who develop thrombosis before the age of 50. In 1993, a new genetic risk factor was discovered: activated protein C resistance which is due to the Q506 mutation in factor V. This defect represents the most prevalent abnormality of inherited thrombophilia, affecting 20 to 40% of thrombophilic patients. Interestingly, hyperhomocysteinemia, known as potentially predisposing to arterial disease, was also recognized as a risk factor for venous occlusive disease. Several genes encoding homocystein metabolism enzymes, such as cystathionine beta-synthase or methylenetetrahydrofolate reductase are concerned. Establishment of a causal association between the presence of a biological abnormality and the occurrence of thrombosis may lead to an adapted prophylaxis whatever the risk situation.

Hypercoagulable states are characterized by an increased risk for developing venous and arterial thrombosis. This situation is the consequence of inbalance of the hemostatic activity (fibroinformationfibrinolysis). Primary and secondary hypercoagulable states are reviewed and clinical situations mandatory for a laboratory evaluation are discussed.

The protein C (PC) pathway is a major anticoagulant system, the role of which is evidenced by the incidence of thrombotic events occurring in patients presenting PC or PS deficiencies. However, the regulation mechanism of this system is not yet well understood. A part of the thrombin produced during the coagulation process interacts with the protein thrombomodulin on the endothelium surface. This thrombin-thrombomodulin complex converts PC to activated PC (APC). APC then interacts with its cofactor protein S on phospholipid surfaces, and proteolytically inactivates factors Va and VIIIa, thus limiting the thrombin formation. Factor V mutation at position 506 (replacement of an Arg by a Gln) results in a decrease of factor Va inactivation rate by APC and has been recently described as a thrombosis risk factor. This "APC resistance" has been found in 15 to 20% of patients with antecedents of thromboembolic events. The PC pathway is also linked to the inflammatory reaction. A fraction of circulating PS is complexed to a regulatory protein of the complement system, the C4b binding protein (C4bBP) and only the free PS is active. An increase in the C4bBP level results in an elevation of bound PS, and as a consequence in a decrease of the free active form of PS. Moreover, endotoxins and cytokins inhibit the expression of both TM and the recently described PC cellular receptor. Under these conditions, a stimulation of tissue factor expression occurs on activated monocytes and endothelials cells surface. APC also modulates inflammatory response, through preventing tumor necrosis factor production. Thus, in the absence of PC, inflammation leads to an increased thrombin formation. This suggests that functions of PC system components are not only implicated in the regulation of the coagulation process, but also in inflammatory reactions and cellular proliferative responses.

We report the case of a patient who was admitted in hospital for evaluation of a superior vena cava thrombosis. The patient exhibited an activated protein C resistance due to an arginine-506 mutation in factor V. Thoracic CT-scan showed a non-compressive complete superior vena cava thrombosis. Other investigations revealed a pleural effusion associated with an ovarian tumor. Pathological data of pleural biopsies showed a papillar carcinoma. Ovarian neoplasia revealed by a paraneoplasic syndrome was diagnosed. Treatment associated cyclophosphamide and carboplatin with anti-K-vitamin was administrated, with a complete remission and disappearance of superior vena cava thrombosis at 27 months of evolution. At this date, we observed a local pelvis recurrence which was treated with paclitaxel associated with surgery.

Resistance to the activation of protein C is a recently discovered constitutional anomaly of coagulation which is responsible for thromboembolic events in young subjects. We report a case in a 26 year old man who presented with pulmonary embolus. Laboratory data was characterised by an absence of any lengthening of the activated cephaline time after adding purified activated exogenous Protein C. The confirmation of this anomaly is provided by the evidence of a mutation Arg 506 to Gln of Factor 5. The outcome is favourable with treatment by Heparin then by anti-Vitamin K.

Thromboangiitis obliterans is a segmental obliterating inflammatory arteritis, usually found in young (below 40) smoking males. Its diagnosis relies on patient history, clinical features, arterial angiography, and more rarely on pathological findings, though none of these is specific of the disease, and on the absence of other diseases such as early atheroma, thromboembolic processes, vascular malformation, trauma, collagen or blood disorders. Raynaud's phenomenon, digital arteritis, superficial and often migrating venous thromboses are further arguments for the disease. However, such associations can also occur during other diseases, especially congenital or acquired deficits in coagulation factors (antiphospholipid syndrome, S protein deficiency...). In our patient with suspected thromboangiitis obliterans, the occurrence of superior longitudinal and right lateral sinus thrombosis led to the discovery of a qualitative C protein defect. This observation stresses the need for careful elimination of a coagulation disorder before confirming the diagnosis of thromboangiitis obliterans.

Mesenteric ischemic process can lead to bowel infarction or indolent low-grade ischemia. Inherited thrombophilia represents about 30 to 40% of mesenteric vein thrombosis. Analysis of thromboembolism sites occurring during genetic defect of coagulant factors showed that mesenteric thrombosis is the third localization after lung and legs, in equal incidence with cerebral thrombosis. The genetic defects known to be associated with thrombophilia, as deficiencies of protein C, protein S, antithrombin III, and dysfibrinogenemia, are discussed. A special interest is devoted to resistance to activated protein C. Acquired diseases, as myeloproliferative disease or paroxysmal nocturnal hemoglobinemia, inducing thrombosis are also discussed. Recent advances in both basic and clinical research have provided new insights that may be integrated into diagnostic and therapeutic practices.

Thrombophilia is characterized by an inherited or acquired defect in the blood coagulation pathway leading to an increased risk for thrombosis. The etiological approach following confirmed venous thrombotic events should rule out medical or chirurgical risk factors. Thrombophilia should be sought by laboratory tests. The recent discovery of a blood coagulation defect: inherited resistance to activated protein C which is found to 20% of patients with former thrombotic events has changed current laboratory approach. Deficiencies of one of the anticoagulant proteins (antithrombin III, protein C, protein S) are found in 10% of the patients, similar to the frequency of antiphospholipid antibodies. These tests may be difficult to interpret immediately after the thrombotic event because of various factors such as inflammatory states or anticoagulant treatments. Therefore this abnormal tests should be confirmed on a later sample analysis far from the event. The discovery of an inherited blood coagulation pathway defect may affect the duration of treatment, prophylaxis in situations with circumstantial risk factors and requires familial analysis. Inherited resistance to activated protein C may be associated with another inherited defect leading to an increased risk for thrombosis.

The clinical history of well-documented personal or familial episodes of thromboembolism with systematic construction of a genealogical tree orients the diagnosis of hereditary or acquired thrombophilia. The presence of favorable medical or surgical conditions for pulmonary embolism (surgical operation, prolonged bed rest, oral contraception, pregnancy, etc) are commonly observed in thrombophilia. Young age, under 40, at the time of the first episode, the recurrent nature of thromboses and a positive family history are three criteria in favour of the diagnosis of hereditary thrombophilia. Laboratory tests should be performed, if possible anticoagulant therapy, or taking into account its effect on the results, heparin reducing the antithrombin level and the oral anticoagulants those of proteins C and S and affecting the "classical" test of resistance to activated protein C. This abnormality is observed in nearly 20% of patients with previous thromboembolism in familial thrombophilia whereas it is twice less common in deficits of antithrombin, protein C and protein S. The other more or less acknowledged causes, alteration of plasminogen, dysfibrinogenaemia, homocysteinaemia, particular blood diseases, indicating systematic association of a full blood count with blood clotting tests, are much more rare. Of the acquired thrombophilias, the commonest is the presence of circulating anticoagulant and/or anticardiolipine antibodies, these two conditions also requiring systematic investigation. Biological examinations for determining the cause of unexpected pulmonary embolism is essential but should not delay instauring treatment. It should be associated with a familial enquiry if the patient has a hereditary thrombophilia. Interpretation of the results should obey the rule of the 3 cs: is the biological abnormality the cause, a coincidence or the consequence of the affection?

Eighteen patients with an acute thrombosis of the splanchnic veins were reviewed. Most of apparently idiopathic cases of splanchnic vein thrombosis are related to an increased coagulation related to a congenital or acquired defect of haemostasis. The aim of this study was to assess the effects of a new and effective treatment. Nine male and 9 female patients (range of age: 19 to 81 years) experienced a mesenteric venous thrombosis. There were 14 mesenteric vein thromboses with infarction, two transient mesenteric venous ischaemias without bowel infarction and two acute thromboses of the splanchnic veins without bowel ischaemia. A coagulopathy was detected in seven patients: oral contraception, protein C (PC) or antithrombin III (AT III) congenital deficiencies, acquired deficiency of AT III, PC and protein S (PS), polycythaemia in the post-partum period and primary myeloproliferative disorder. No coagulopathy was associated with thrombosis in eight cases: mesenteric haematoma, splenomegaly, cirrhosis, appendicectomy, cholescytectomy, chronic heart failure, treatment with beta-adrenergic receptor antagonist and digitalis, stenosis of the portal anastomosis after liver transplantation. Twelve patients required surgery: eight intestinal bowel resections with immediate anastomosis, four resections without immediate anastomosis. Only one patient underwent a second look for a repeat bowel resection. No death occurred in the early postoperative period and 17 out of 18 patients were alive after 12 years. An oral anticoagulant therapy was undertaken from two months to seven years. However, three patients suffered a recurrent thrombosis. Two of them required a long-term anticoagulation. Six patients experienced a portal hypertension and oral anticoagulants were discontinued in three of them because of bleeding oesophageal varices. Six patients were treated only by unfractionated heparin (UFH) or low molecular weight heparin (LMWH) followed by oral anticoagulants. After laparotomy, two were only treated with UFH without any bowel resection, as mesenteric venous ischaemia was too extensive. These observations suggest that the choice between an appropriate medical or surgical treatment is important and must be discussed. Since 1989, the therapeutic choice has been modified by ultrasonography and contrast enhanced computed tomographic scan which confirms diagnosis, allows to follow up and check the effects of anticoagulation and to choose the time for surgery. When the diagnosis is established and the patient's risk is low, the IU . kg(-1) . d(-1) to obtain an antifactor Xa activity between 0.3 and 0.6 antiXa IU mL(-1). When the diagnosis is uncertain and the patient's risk if high a laparotomy is required.(ABSTRACT TRUNCATED AT 400 WORDS)

The Buschke-Ollendorff syndrome (BOS) is a rare connective tissue disorder inherited in an autosomal dominant pattern characterized by cutaneous lesions, dermatofibrosis lenticularis disseminata, and osteopoikilosis. We report a new case of this syndrome in a 66 year old man, interesting by its association with a protein C deficiency, another rare genetically transmitted disease. Diagnosis of the BOS is difficult on the mere cutaneous lesions; it is therefore important to systematically practice bone X-rays in the presence of atypical pseudoxanthoma elasticum, disseminated collagenoma or disseminated connective tissue or elastic nevi. The radiologically detectable osteopoikilotic bone lesions, evoking Paget's disease, easily sign the diagnosis. In our case, the association of a protein C deficiency with the BOS may not be fortuitous because both the elastin and protein C genes are localized on chromosome 2q.

Six patients aged 3 to 14 years with lower limb vein thrombosis were included in a prospective study of deficiencies in physiological coagulation inhibitors. The laboratory evaluation included standard hemostasis tests, tests for circulating anticoagulants, immunological and functional assays of protein C, protein S, and antithrombin III, and a study of fibrinolysis. A qualitative protein S deficiency with decreased fibrinolysis and protein C deficiency were found. The family study detected asymptomatic heterozygotes in both families investigated. No antithrombin III deficiency or circulating anticoagulants were found.

A case of unexpected cardiac arrest occurring in a 17-year-old male patient is reported. The patient had been admitted after sustaining hand trauma. A first emergency surgical procedure was carried out, followed about three weeks later by another one. No incidents occurred during or after either of these two operations. A third procedure was required about two months after the accident (free toe graft to the thumb of the left hand). The twelve-hour operation was carried out under general anaesthesia and axillary block. The patient was given intravenous heparin (800 IU.h-1) during the procedure on the arm. The patient recovered quickly, and was extubated before his transfer to the recovery room. Fifteen minutes later, the patient's heart rate decreased to 40 b.min-1, followed by a transient cardiorespiratory arrest. The suspicion of pulmonary embolism was confirmed by pulmonary scintigraphy. Thrombolysis was carried out with 2,000 IU.kg-1.h-1 of urokinase for a 72 h period, combined with continuous heparin administration (16 to 36 x 10(3) IU.day-1). The patient recovered after one week. No thrombophlebitis was found for origin of the emboli. Biological investigations carried out both before and after 10 minutes of anoxia revealed a normal fibrinolytic system, but a deficit in protein C (62% antigen, 64% activity). Two years after the episode of pulmonary embolism, the patient, still taking acenocoumarol, remained free from any sequela. Current perioperative management of patients with a known protein C deficit is discussed.

The authors report the case of a 51 year-old man, without any personal or familial history of thromboembolism, presenting with abdominal pain. Portal vein thrombosis was demonstrated by ultrasonography and arteriography. The patient had neither esophageal varices or congestive gastropathy. No cause for portal vein thrombosis was detected. Type I protein C deficiency was demonstrated in this patient as well as in his asymptomatic sister. The presence of a (fortuitously?) associated increase in platelet aggregability initially led to a trial regimen of aspirin (300 mg per day); abdominal pain resolved, and a partial regression of portal vein thrombosis was demonstrated on ultrasonograms six months later; no further complications occurred during the 4-year follow-up period. The 13 previously published cases of protein C deficiency-associated portal vein thrombosis are reviewed.