[Colonic pseudotumoral involvement as an expression of severe plasminogen deficiency]. / Compromiso pseudotumoral colónico como expresión de déficit grave de plasminogéno.

Plasminogen deficiency is a very rare multisystem entity that affects different tissues of the economy through the deposition of fibrin-rich pseudomembrane and determines a heterogeneous and diverse clinical presentation. It is transmitted in an autosomal recessive manner by mutations of the PLG gene on chromosome 6 and can be divided into hypoplasminogenemia or type I and dysplasminogenemia or type II, the latter not related to clinical pathology. Severe plasminogen deficiency has a prevalence of 1.6 individuals per million inhabitants and although it can be diagnosed in adulthood, the most severe symptoms are observed in infants and children. The most common form of onset is the so-called woody conjunctivitis, characterized by fibrin membranes that are deposited on the eyelids since childhood, causing exophytic lesions that affect vision. It can also affect other mucous membranes such as the gingival, respiratory, oropharyngeal, digestive and genital mucosa, among others. We present a rare case of severe plasminogen deficiency with conjunctivitis and woody cervicitis who was admitted with clinical acute abdominal symptoms, associated with a tumor mass due to pseudomembranous deposition in the ascending colon that simulated inflammatory bowel disease and resolved spontaneously.

La deficiencia de plasminógeno es una entidad multisistémica, muy infrecuente, que afecta diferentes tejidos de la economía mediante el depósito de pseudo membranas ricas en fibrina y que determina una presentación clínica heterogénea y diversa. Se transmite en forma autosómica recesiva por mutaciones del gen PLG del cromosoma 6 y se puede dividir en hipoplasminogenemia o tipo I y displasminogenemia o tipo II, esta última no relacionada con patología clínica. El déficit grave de plasminógeno tiene una prevalencia de 1.6 individuos por millón de habitantes y si bien puede diagnosticarse en edad adulta, los síntomas más graves se observan en lactantes y niños. La forma de inicio más común es la denominada conjuntivitis leñosa, caracterizada por membranas de fibrina que se depositan en los parpados desde la infancia, provocando lesiones exofíticas que afectan la visión. También puede afectar otras mucosas como la gingival, respiratoria, orofaríngea, digestiva y genital entre otros. Presentamos un raro caso de deficiencia grave de plasminógeno con conjuntivitis y cervicitis leñosa que ingresó con un cuadro de abdomen agudo clínico, asociado a una masa tumoral por depósito de pseudomembranas en el colon ascendente que simuló una enfermedad inflamatoria intestinal y que se resolvió espontáneamente.

von Willebrand Disease and other hereditary haemostatic factor deficiencies in women with a history of postpartum haemorrhage.

INTRODUCTION: Postpartum haemorrhage (PPH) is the main cause of maternal morbidity and mortality globally, but it is far more important in non-developed countries. PPH represents 25% of all maternal deaths worldwide. Women with von Willebrand disease (VWD) and other inherited haemorrhagic disorders are at increased risk of PPH. Our aim was to establish a probable association of severe PPH in women with a history of haemostatic abnormalities. METHODS: An observational, controlled study of adult women with a one or more episodes of severe PPH requiring treatment in an intensive care unit or >10 units of blood products during the 24-hour period after diagnosis and their controls. The tests performed were blood cell count, blood group, renal, viral, liver function and haemostatic tests, fibrinogen, activity of the plasma factors and specific test to diagnose and classify VWD. RESULTS: We included 124 women with 133 PPH events and their controls. The median age at the first event was 25.5 years old. Results were significantly different between the groups in terms of fibrinogen concentration, VWF:Ag, VWF:RCo and FVIII. A specific diagnosis was established in 69 (55.6) and 4 (3.2%) patients in the PPH group and controls, respectively. Of 61 patients with VWD, 57 had type 1, two had type 2A, and another two had type 2B. CONCLUSION: Our results show a relationship between PPH and inherited haemostatic disorders. VWD was the most frequent diagnosis. Appropriate and opportune diagnosis before pregnancy of inherited haemostatic disorders may be important to effectively prevent and treat PPH.

Trastornos de la hemostasia durante la gestación / Hemostasia disorders during pregnancy

Se realizó una revisión de la literatura en relación con los trastornos hemorrágicos durante la gestación y se mencionan los cambios hematológicos fisiológicos que ocurren durante el embarazo y el puerperio. La conocida teoría de la coagulación como un proceso en cascada no tiene vigencia en la actualidad, sino que esta ha dado paso a la moderna teoría celular de la coagulación. Se describen también los criterios diagnóstico y terapéutico en las hemorragias obstétricas por incoagulabilidad sanguínea (HOICS). Al analizar el cuadro clínico y los resultados de laboratorio, se puede realizar un diagnóstico seguro de la HOICS que se presenta. La disminución de las plaquetas en sangre, constituye con frecuencia en los casos de HOICS la alteración inicial, el factor V de la coagulación siempre está disminuido, mientras que el factor VIII de la coagulación, generalmente se encuentra elevado. El uso de heparina de alto y bajo peso molecular, y de factores de la coagulación para el tratamiento de las HOICS ha sido controvertido. Se ha recomendado en estos casos la administración de sangre fresca, plasma fresco, plasma homólogo, crioprecipitados y concentrado de plaquetas. Actualmente, se vienen remplazando estas conductas terapéuticas por el uso del FVIIa recombinante, el cual puede asociarse con el misoprostol. La evacuación de la cavidad uterina tan pronto como sea posible constituye una medida necesaria en algunas pacientes

A literature review was performed in relation to hemorrhagic disorders during pregnancy signaling the physiologic and hematologic changes occurring at pregnancy and the puerperium. The well-known theory of coagulation as a cascade process has not validity at present time, but that this one gave way to the modern cellular theory of coagulation. The diagnostic and therapeutical in blood incoagulability obstetrics hemorrhages (BIOH). Analyzing the clinical picture and the lab results, it is possible to make an accurate diagnosis of present BIOHs. The blood platelet decrease, frequently in BIOH cases is the first alteration, the V coagulation factor, in general is always decreased, whereas the VIII coagulation factor is in general increased. The high and low weight heparin use and of coagulation factors for treatment of BIOHs has been controversial. In such cases it is recommended the administration of fresh blood, fresh plasma, the homologous plasma cryoprecipitates and platelet concentrates. Nowadays these therapeutical behaviors have been replaced by the use of recombinant FVIIa, which may be associated with the Misoprostol. The uterine cavity evacuation as soon as possible is a needed measure in some patients.

High prevalence of bleeders of unknown cause among patients with inherited mucocutaneous bleeding. A prospective study of 280 patients and 299 controls.

BACKGROUND AND OBJECTIVES: Mucocutaneous bleeding (MCB) is the main expression of inherited disorders of primary hemostasis. However, the relative prevalence of these disorders, their clinical differential diagnosis, and the proportion of patients with MCB of unknown cause (BUC) after an initial comprehensive laboratory testing are unknown. DESIGN AND METHODS: We studied prospectively 280 consecutive patients with MCB and 299 matched controls, using strict inclusion and exclusion criteria. A single physician recorded the clinical data in a bleeding score and estimated the severity of bleeding in clinical categories. Laboratory criteria for the diagnosis of von Willebrand's disease (VWD) and platelet function defects were established from reference values derived from controls. RESULTS: Fifty patients (17.9%) had VWD (type 1VWD=45, type 2=5). Platelet function defects and mild clotting factor deficiencies were found in 65 (23.2%) and 11 (3.9%) patients, respectively. Thirteen (11.5%) patients had combined defects. The remaining 167(59.6%) patients had BUC, with prolonged bleeding time in 18.6% as their only abnormality. All these disorders, including BUC, were clinically undistinguishable. Moreover, no relationship was found between the severity of bleeding and VWF/platelet function variables. INTERPRETATION AND CONCLUSIONS: The diagnostic efficacy of a first laboratory testing in patients with hereditary MCB is 40.4%. Most patients have a disease(s) of high prevalence but unknown pathogenesis. Concurrent bleeding disorders in the same patient are frequent. Our results support the proposal that low plasma VWF levels, but also platelet function defects, should be considered risk factors rather than unequivocal causes of hemorrhages.

[Thrombophilic disorders in children and adolescents with portal vein thrombosis]. / Distúrbios trombofílicos em crianças e adolescentes com trombose da veia porta.

OBJECTIVE: To determine the frequency of protein C, protein S and antithrombin deficiency, and factor V Leiden, prothrombin G20210A, and methylenetetrahydrofolate reductase C677T mutations in children and adolescents with portal vein thrombosis, as well as assessing the hereditary character of this disorders. METHODS: A two-year study was carried out to determine the frequency of thrombophilic disorders in children and adolescents with portal vein thrombosis (n = 14), their parents (n = 24), and two control groups, one age-matched children and adolescents free of liver disease (n = 28) and another group with cirrhosis (n = 24). The portal vein thrombosis patients were investigated by clinical and laboratory means, esophagogastroduodenal endoscopy and liver biopsies. The presence of portal vein thrombosis was assessed by Doppler ultrasonography and/or angiographic analysis. RESULTS: The frequency of protein C, protein S and antithrombin deficiency was 6/14 (42.9%) (p < 0.05 versus controls), 3/14 (21.4%) (p > 0.05) and 1/14 (7.1%) (p > 0.05) of children and adolescents with portal vein thrombosis, respectively. The frequency of protein C, protein S and antithrombin deficiency in cirrhotic patients was 14/24 (58.3%), 7/24 (29.2%) and 11/24 (45.8%), respectively (p < 0.05 versus controls free of liver disease). None of the portal vein thrombosis parents or controls presented protein C, protein S or antithrombin deficiency. One portal vein thrombosis patient and one control (p = 0.999) presented prothrombin G20210A mutation. The homozygous form of methylenetetrahydrofolate reductase C677T mutation was observed in 3/14 (21.4%) patients with portal vein thrombosis and in 5/28 (17.9%) (p = 0.356) controls. None of the patients or controls presented the factor V Leiden. CONCLUSION: Half of the children and adolescents with portal vein thrombosis presented deficiency of one or more coagulation inhibitor proteins, mainly protein C, but this deficiency does not seem to be an inherited condition. The hereditary prothrombotic disorders do not seem to play a vital role in thrombosis in patients with portal vein thrombosis of this study. In the cirrhotic patients, there was a higher frequency of protein deficiency when the disease was more intense.

Inherited complete factor I deficiency associated with systemic lupus erythematosus, higher susceptibility to infection and low levels of factor H.

Here we describe two new cases of complete deficiency of factor I (fI) in two sisters from a consanguineous Brazilian family. The eldest sibling (20-year-old) developed systemic lupus erythematosus (SLE) early during childhood while the youngest had been committed on several occasions owing to repeated infections although she was asymptomatic for auto-immune diseases. We also detected lower concentrations of C3 and factor B in both sisters. Biological functions dependent on complement activation such as the production of opsonins and killing of phagocytozed micro-organisms, chemotactic factors and haemolytic activity were all significantly reduced in both probands. Consistent with the absence of fI and low levels of fH, a deregulated production of C3b was observed by bidimensional electrophoresis in sera of both the probands.

Budd-Chiari syndrome associated with coagulation abnormalities in a child with carbohydrate deficient glycoprotein syndrome type Ix.

A 6-year-old male patient presented with Budd-Chiari syndrome and glycoprotein abnormalities associated with carbohydrate deficient glycoprotein syndrome type I with yet unidentified molecular defect (type Ix). Budd-Chiari syndrome most likely developed after hepatic venous thrombosis caused by coagulation abnormalities resulting from hypoglycosylation and functional impairment of anticoagulant proteins.