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Budd-Chiari syndrome in a paroxysmal nocturnal hemoglobinuria patient with previous cerebral venous thrombosis
No full textParoxysmal nocturnal hemoglobinuria (PNH) is a rare
clonal stem cell disorder characterized by intravascular
hemolytic anemia that results from the clonal expansion of
hematopoietic stem cells harboring somatic mutations in an
X-linked gene, termed PIG-A (phosphatidylinositol glycan
class A). PIG-A mutations block glycosylphosphatidylinositol (GPI) anchor biosynthesis, resulting in a deficiency
or absence of all GPI-anchored proteins on the cell surface.
CD55 and CD59 are GPI-anchored complement regulatory
proteins. Their absence on PNH red cells is responsible for
the complement-mediated intravascular hemolysis, leading
to the release of free hemoglobin, which contributes to many
of the clinical manifestations of PNH including fatigue,
pain, esophageal spasm and possibly serious thrombotic
episodes [1]. Allogeneic hematopoietic stem cell transplantation is the only curative therapy for PNH. The
complement inhibitor eculizumab, a humanized monoclonal
antibody against C5, that inhibits terminal complement
activation, recently approved in the US, has been shown to
reduce hemolysis, decrease the erythrocyte transfusion
requirements and the risk for thrombosis, and to improve
quality of life of PNH patients [2, 3]. Major morbidity and
mortality with PNH are often ascribed to the development of
venous thromboembolism (VTE) [1–6], and several patients
have recurrent thromboses [7]. VTE in PNH patients occur
mostly at unusual sites. Data from a recent review report
hepatic vein thrombosis, leading to Budd-Chiari syndrome
(BCS), as the most frequent (40.7%) thrombotic complication, accounting for the majority of deaths [8], followed by
cerebral vein and sinus thromboses, superior sagittal sinus
being the most frequently involved site [8]. Inherited
thrombophilia may increase the risk of serious thromboembolic events in PNH patients [9]. In patients experiencing
VTE, early anti-thrombotic therapy (heparin, thrombolysis)
aimed to limit the extension of thrombosis, or to dissolve
formed thrombi, should improve the prognosis of this severe
complication. PNH patients suffering from VTE should be
treated with anticoagulant drugs indefinitely [1]. Thrombocytopenia often complicates PNH, and this issue must be
addressed when an anticoagulation management plan is
formulated [1]. Recurrent, life-threatening thrombosis
merits consideration for bone marrow transplantation
(BMT) [1]. Over the past few years significant advances in
other therapeutic approaches, such as transjugular intrahepatic portosystemic shunt (TIPS), have contributed to the
improvement of survival in this setting [8].
We report the case of a 29-year-old woman, R. D. The
family history was negative for VTE and cardiovascular
disease. She was a non-smoker. And had been slightly
overweight since childhood. When she was 19 years old, an
isolated moderate thrombocytopaenia (50,000/mmc) was
detected although in the absence of bleeding. As idiopathic
thrombocytopaenia was diagnosed, she was treated with
long-term steroids, with an improvement in the platelet
count (120,000/mmc). At the age of 27, while on oral
contraceptives for 3 months, she experienced a sudden
occurrence of headache and visual loss, followed by seizures and coma. A computed tomography (CT scan)
showed multiple cerebral venous thromboses. Screenings
A. Tufano (&) N. Macarone Palmieri E. Cimino
A. M. Cerbone
Regional Reference Centre for Coagulation Disorders,
Department of Clinical and Experimental Medicine,
Federico II University of Naples, Via S. Pansini, 5,
80131 Naples, Italy
e-mail: [email protected]
F. Alfinito
Division of Hematology, Federico II University of Naples,
Via S. Pansini, 5, 80131 Naples, Italy
123
Intern Emerg Med (2009) 4:75–77
DOI 10.1007/s11739-008-0182-7for congenital (antithrombin, protein C, protein S, factor V
Leiden, prothrombin G20210A mutation, C677T MTHFR
variant) and acquired (Lupus anticoagulant, antiphospholipid antibodies) thrombophilic abnormalities were negative.
At that time, according to the available clinical records,
she did not receive anticoagulant drugs, and symptoms
improved after diuretics and steroid administration.
Two years later, when she was 29 years of age, the
patient was admitted to our hospital for recurrent abdominal pain, fever and pancytopaenia (WBC 4,000/mmc; Hb
9 g/dl; platelets 61,000/mmc). Steroid treatment had been
withdrawn some weeks before the admission. Laboratory
testing confirmed anaemia (9.8 g/dl) and a low platelet
count (60,000/mmc), and also showed an increased LDH
(1605 IU/L) ALP (137 IU/L) and cGT (112 IU/L) levels
and reduced haptoglobin. An abdominal CT scan showed
hepatic and splenic enlargement with ascites and signs of
hepatic outflow obstruction, consistent with a Budd-Chiari
syndrome (Fig. 1). Lupus anticoagulant and antiphospholipid antibodies were still negative. Homocysteine levels
were normal. Cytofluorimetric investigation of peripheral
blood cell immunophenotype showed abnormalities of
complement regulatory proteins, consistent with the diagnosis of PNH [10]: 80% of red blood cells were CD59
deficient, 90% of granulocytes lacked CD 68b and 95% of
monocytes did not show CD14 on cell membrane. Almost
all hemopoesis was clonal. Bone marrow aspirate showed
dysplastic features.
Because of the thrombocytopenia, and while the patient
was under evaluation for BMT, treatment with oral anticoagulants was delayed, and therapy with full-dose
enoxaparin (100 IU/Kg bid) was started. Progressive
splenic enlargement and bone marrow failure resulted in
further reduction of the platelet count over the following
three months (30,000/mmc); therefore, heparin dosage was
reduced to 100 IU/Kg/d in order to avoid hemorrhagic
complications. Six months later she experienced recurrent
abdominal pain and ascites, compatible with a recurrence
of the Budd-Chiari syndrome, and fatal hepatic failure. Her
severe clinical condition hampered surgical or radiologic
therapeutic approaches.
Another PNH patient with a history of cerebral venous
thrombosis and Budd-Chiari syndrome is described in a
case-report published in 2005 [11]. The authors present the
case of a 26-year-old man with a previous diagnosis of
apparently idiopathic cerebral vein thrombosis, who
developed hepatic venous thrombosis, and who had laboratory tests suggestive of PNH 9 months later. This patient
underwent a TIPS, but experienced 1 month later an episode of stent blockage treated with balloon dilatation and
restenting.
In conclusion, our case report highlights that PNH
should be considered in patients with venous thrombosis at
unusual sites, especially if associated with haemocromocytometric abnormalities. Antithrombotic treatment in this
setting is mandatory, but a careful risk-to-benefit ratio
evaluation should be taken into account. A TIPS procedure
may be a useful therapeutic option for PNH patients with
Budd-Chiari syndrome, but caution is needed to prevent
stent occlusion
Increased binding of fibrinogen to platelets in diabetes: the role of prostaglandins and thromboxane.
No full textThe infectious burden in atherothrombosis.
No full textPathogenesis of atherosclerosis involves multiple mechanisms, including imbalanced lipid metabolism, disturbed equilibrium of the immune response, and chronic inflammation of the artery wall. Several reports have shown a relationship between the development of atherosclerosis and the presence of infectious diseases, widely occurring in the general population, often chronic and/or asymptomatic. Beyond Chlamydia pneumoniae, a large number of infectious agents have been linked with an increased risk of vascular disease, with variable strength of supporting data: Porphyromonas gingivalis, Helicobacter pylori, influenza A virus, herpes virus, hepatitis C virus, cytomegalovirus, and human immunodeficiency virus. Infections may contribute to atherosclerosis either via direct infection of vascular cells or via the indirect effects of cytokines or acute phase proteins induced by infection at " nonvascularo" sites. More recently, investigators reported that the aggregate burden ("infectious burdeno") of these chronic infections, rather than the effects of a single organism, might contribute to atherosclerosis and its thrombotic complications. However, the role of infection, as a proinflammatory cause of atherosclerosis, is still debated in the literature. This article will review available data suggesting a relationship between different infective pathogens and atherothrombosis, the hypothesized mechanisms, and the potential role for antimicrobial treatment
Prevention of venous thromboembolism in medical patients with thrombocytopenia or with platelet dysfunction: a review of the literature.
No full textCurrent guidelines for venous thromboembolism (VTE) primary prophylaxis are based on randomized clinical trials that exclude subjects at a potentially high bleeding risk. Thus no specific recommendation/algorithm for pharmacological prophylaxis in patients with thrombocytopenia and/or platelet dysfunction is available. Because at least 25% of subjects admitted to medical departments exhibit these conditions, information on this subject is provided here to optimize their VTE prophylaxis. Low platelet number/function and clotting abnormalities are common in patients with liver cirrhosis. However, these patients have a high incidence of portal and idiopathic venous thromboses, implying that cirrhotic coagulopathy does not protect against thrombosis. At variance with severe thrombocytopenia (50,000/mu L) should not interfere with VTE prevention decisions. In severe thrombocytopenia, prophylaxis should be considered on an individual basis, however. In patients with antiphospholipid antibodies and thrombocytopenia, a thrombotic tendency is usually associated rather than a bleeding risk. VTE prophylaxis in high-risk conditions is thus suggested in these patients. Except in cases with contraindications to anticoagulation, antithrombotic prophylaxis should be always considered in hospitalized cancer patients with thrombocytopenia, especially in those with hematologic malignancies and multiple VTE risk factors. Aspirin treatment is not as effective as heparins in lowering the risk of VTE. Studies in stroke suggest that thromboprophylaxis with heparins is safe in patients with ischemic stroke undergoing aspirin treatment. The need for VTE prophylaxis in patients on chronic treatment with aspirin and/or clopidogrel should be evaluated after assessing the individual risk-benefit ratio
Going Beyond Counting First Authors in Author Co-citation Analysis
Get PDFThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Variations on the Author
Get PDF“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
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