The Mode of Inheritance of PTA Deficiency: Evidence for the Existence of Major PTA Deficiency and Minor PTA Deficiency

Rapaport, Samuel I.; Proctor, Robert R.; Patch, Mary Jane; Yettra, Maurice

doi:10.1182/blood.v18.2.149.149

Cited by 166 publications

(88 citation statements)

References 6 publications

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“…Prekallikrein functional levels were performed by a microtiter amidolytic assay using a chromogenic substrate [S-2302 (Pro-Phe-Arg-p-nitroanilide); Chromogenix, Mölndal, Sweden] as described previously (13,14). HK coagulant activity was determined by a slight modification of the method described by Proctor and Rapaport (15,16). We used human total kininogendeficient plasma (17).…”

Section: Contact System Protein Functional Assaysmentioning

confidence: 99%

Interactions between bradykinin (BK) and cell adhesion molecule (CAM) expression in peptidoglycan‐polysaccharide (PG‐PS)‐induced arthritis

et al. 2004

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Bradykinin (BK), a vasoactive, proinflammatory nonapeptide, promotes cell adhesion molecule (CAM) expression, leukocyte sequestration, inter-endothelial gap formation, and protein extravasation in postcapillary venules. These effects are mediated by bradykinin-1 (B1R) and-2 (B2R) receptors. We delineated some of the mechanisms by which BK could influence chronic inflammation by altering CAM expression on leukocytes, endothelium, and synovium in joint sections of peptidoglycan-polysaccharide-injected Lewis rats. Blocking B1R results in significantly increased joint inflammation. Immunohistochemistry of the B1R antagonist group revealed increased leukocyte and synovial CD11b and CD54 expression and increased CD11b and CD44 endothelial expression. B2R antagonism decreased leukocyte and synovial CD44 and CD54 and endothelial CD11b expression. Although these findings implicate B2R involvement in the acute phase of inflammation by facilitating leukocyte activation (CD11b), homing (CD44), and transmigration (CD54). Treatment with a B2R antagonist did not affect the disease evolution in this model. In contrast, when both BK receptors are blocked, the aggravation of inflammation by B1R blockade is neutralized and there is no difference from the disease-untreated model. Our findings suggest that B1R and B2R signaling show physiologic antagonism. B1R signaling suggests involvement in down-regulation of leukocyte activation, transmigration, and homing. Further studies are needed to evaluate the B1 receptor agonist's role in this model.

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Section: Contact System Protein Functional Assaysmentioning

confidence: 99%

Interactions between bradykinin (BK) and cell adhesion molecule (CAM) expression in peptidoglycan‐polysaccharide (PG‐PS)‐induced arthritis

et al. 2004

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“…People with partial de®ciency have factor XI:C levels between 15 and 20 U dL 71 and the lower limit of the normal range, which is variably de®ned. Many hospitals quote 50 U dL 71 , but when the normal range is derived by taking two standard deviations either side of the mean of a group of normals, values range between 63 U dL 71 [10] and 80 U dL 71 Coagulation is initiated at a site of vessel damage when factor VIIa is exposed to tissue factor. Factors VIII, IX, and XI are required for the production of additional factor Xa due to feedback inhibition of the factor VIIa/tissue factor complex by TFPI.…”

Section: Clinical Picture and Inheritancementioning

confidence: 99%

Factor XI deficiency and its management

Bolton‐Maggs

2000

Haemophilia

108

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Factor XI deficiency has a more variable bleeding tendency than haemophilia A or B. Individuals with severe deficiency have only a mild bleeding tendency, which is typically provoked by surgery, but the risk of bleeding is not restricted to individuals with severe deficiency. The bleeding tendency varies between individuals with similar factor XI levels, and sometimes the bleeding tendency of an individual may vary. The reasons for this are not fully understood, although in cases of severe deficiency there is some correlation between phenotype and genotype. Factor XI is activated by thrombin. The role of factor XI in physiological processes has become clearer since this fact was discovered, and the discovery has contributed to a revised model of blood coagulation. Factor XI deficiency occurs in all racial groups, but is particularly common in Ashkenazi Jews. The factor XI gene is 23 kilobases long. Two mutations are responsible for most factor XI deficiency in the Ashkenazi population, but a number of other mutations have now been reported in other racial groups. Individuals with factor XI deficiency may need specific therapy for surgery, accidents, and dental extractions. Several therapies are available which include fresh frozen plasma, factor XI concentrates, fibrin glue, antifibrinolytic drugs, and desmopressin. Each has advantages and risks to be considered. Factor XI concentrate may be indicated for procedures with a significant risk of bleeding especially in younger patients with severe deficiency, but its use in older patients has been associated with thrombotic phenomena. If fresh frozen plasma is to be used it is preferable to obtain one of the virally inactivated products. Fibrin glue is a useful treatment which deserves further study.

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“…Surprisingly, some patients with severe FXI deficiency are asymptomatic even after surgery while others with even mild FXI deficiency exhibit bleeding symptoms [3][4][5][6]. Plasma FXI levels derived from activated partial thromboplastin time (APTT) are useful for diagnosis but are poorly correlated with the clinical bleeding risk of patients [4].…”

Section: Introductionmentioning

confidence: 99%

Thrombin generation in patients with factor XI deficiency and clinical bleeding risk

Rugeri

Quélin²,

Chatard

et al. 2010

Haemophilia

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Factor XI (FXI) deficiency is a rare bleeding disorder. Most patients with FXI deficiency are mild bleeders but certain patients with similar FXI activity exhibit different bleeding phenotype. Routine laboratory assays do not help physicians to estimate the individual bleeding risk in these patients. Thrombin generation test (TGT) is a more comprehensive, global function test of the clotting system. We investigated whether or not the bleeding tendency of patients with FXI deficiency is correlated with features of the TGT. Twenty-four patients with FXI deficiency were divided in two groups: (i) severe bleeders (n = 9) and (ii) mild or non-bleeders (n = 15). All severe bleeders had a personal history of surgery-related severe bleeding. Thrombin generation (TG) was measured in platelet-rich plasma (PRP) using a low concentration of tissue factor 0.5 pm. In patients exhibiting severe bleeding tendency, independently of their FXI level, a dramatically impaired TG was observed. For example, despite a low plasma FXI = 1 IU dl(-1), a clinically non-bleeding individual exhibited normal TG results whereas another patient with severe bleeding history and FXI = 40 IU dl(-1) had a very low TG capacity. Low velocity and delayed TG were the main parameters suggesting a higher bleeding risk. DNA analysis of patients reported eight novel mutations of the FXI gene but neither mutation location nor secretion or not of the variant correlated with the bleeding tendency. The results of this study suggest that TG measurement in PRP may be a useful tool to predict bleeding risk in FXI deficiency and should be studied further in larger prospective clinical studies.

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The Mode of Inheritance of PTA Deficiency: Evidence for the Existence of Major PTA Deficiency and Minor PTA Deficiency

Cited by 166 publications

References 6 publications

Interactions between bradykinin (BK) and cell adhesion molecule (CAM) expression in peptidoglycan‐polysaccharide (PG‐PS)‐induced arthritis

Interactions between bradykinin (BK) and cell adhesion molecule (CAM) expression in peptidoglycan‐polysaccharide (PG‐PS)‐induced arthritis

Factor XI deficiency and its management

Thrombin generation in patients with factor XI deficiency and clinical bleeding risk

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