Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0019087 (hemorrhagic diathesis)
 678 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

This study characterizes a congenital hemorrhagic disorder caused by a platelet function defect with the following features: (1) severely impaired platelet aggregation and fibrinogen or von Willebrand factor (vWF) binding induced by adenosine diphosphate (ADP); (2) defective aggregation, release reaction, and fibrinogen or vWF binding induced by other agonists; (3) normal aggregation and release reaction induced by high concentrations of thrombin or collagen; (4) no further inhibition by ADP scavengers of aggregation, release reaction, and fibrinogen or vWF binding, comparable with those observed for normal platelets in the presence of ADP scavengers; (5) normal membrane glycoprotein (GP) composition and normal binding of the anti-GP IIb/IIIa monoclonal antibody 10E5; (6) no acceleration by ADP of binding of the anti-GP IIb/IIIa monoclonal antibody 7E3; (7) normal platelet-fibrin clot retraction if induced by thrombin or reptilase plus epinephrine, absent if induced by reptilase plus ADP; (8) no inhibition by ADP of the prostaglandin E1-induced increase in platelet cyclic adenosine monophosphate, but normal inhibition by epinephrine; (9) defective mobilization of cytoplasmic Ca2+ by ADP; (10) normal binding of 14C-ADP to fresh platelets, but defective binding of [2-3H]-ADP to formalin-fixed platelets. This congenital platelet function defect is characterized by selective impairment of platelet responses to ADP, caused by either decreased number of platelet ADP receptors or abnormalities of the signal-transduction pathway of platelet activation by ADP.
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PMID:Identification of a new congenital defect of platelet function characterized by severe impairment of platelet responses to adenosine diphosphate. 133 2

Hermansky-Pudlak syndrome is a hereditary disease with an autosomal recessive mode of inheritance, characterized by the triad of tyrosinase-positive oculocutaneous albinism, a hemorrhagic diathesis resulting from storage pool-deficient platelets, and accumulation of ceroid/lipofuscin-like material in various cells and tissues and in the urine. The basic defect in this syndrome remains unknown. It is believed that the primary defect may involve membranes of the platelet-dense bodies and the melanosomes. Recently a defective calcium uptake system and low activities for membrane-associated thioredoxin reductase have been shown in Hermansky-Pudlak syndrome, and their possible role in the pathomechanism of this disorder is discussed.
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PMID:[Hermansky-Pudlak syndrome]. 265 78

Hemophilia B Kashihara is a severe hemorrhagic disorder in which the factor IX antigen is present in normal amounts but factor IX biological activity is markedly reduced. In addition, purified factor IX Kashihara is not activated by purified factor XIa in the presence of calcium ions. Amino acid sequence analysis of one of the tryptic peptides isolated from factor IX Kashihara indicated that Val-182 (equivalent to Val-17 in the chymotrypsin numbering system) had been replaced by Phe. No substitution was found in the members of the catalytic triad His-221, Asp-269, and Ser-365 of factor IX Kashihara. The Val-to-Phe replacement found in factor IX Kashihara appears to sterically hinder the cleavage of Arg 180-Val 181 by factor XIa required for the activation of this zymogen.
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PMID:Blood clotting factor IX Kashihara: amino acid substitution of valine-182 by phenylalanine. 275 73

Rocky Mountain spotted fever (RMSF) or ehrlichiosis was diagnosed in dogs on the basis of specific immunofluorescent testing for each disease. Comparisons between clinical and laboratory findings were made between the 2 diseases. The incidence of RMSF tended to be more seasonal and it affected younger dogs. Purebred dogs appeared to be more susceptible to both diseases. In general, RMSF had a more rapid and severe course of clinical illness than did ehrlichiosis, but acute ehrlichiosis was difficult to differentiate from RMSF. Both diseases were characterized by fever, depression, lymphadenopathy, and signs of neurologic dysfunction; petechial hemorrhages or other signs of hemorrhagic diathesis were evident only in a small proportion of cases. Anemia, leukopenia, and thrombocytopenia were more common in dogs with ehrlichiosis, whereas those with RMSF more often had leukocytosis and thrombocytopenia. Hypoalbuminemia was found in dogs with both diseases, but those with ehrlichiosis usually had concurrent hyperglobulinemia. High serum alkaline phosphatase activity and serum cholesterol concentration, and low serum calcium concentration were more common in dogs with RMSF than with ehrlichiosis. Rising serum titers or positive direct immunofluorescence for Rickettsia rickettsii in skin biopsy specimens were used to confirm RMSF, whereas a single serum titer for Ehrlichia canis enabled detection of ehrlichiosis. In the absence of neurologic deficits and when dogs were treated with tetracycline, dogs with RMSF made a more rapid and consistent recovery than did dogs with ehrlichiosis.
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PMID:Rocky Mountain spotted fever in dogs and its differentiation from canine ehrlichiosis. 397 6

A severe hereditary hemorrhagic diathesis in Simmental cattle has been identified in North America. Platelet numbers and coagulation profiles of affected cattle are normal. We have further characterized the severe dysfunction of platelet aggregation. All agonists tested elicited normal shape change. Aggregations in response to ADP, A23187, and collagen were absent. Aggregations were decreased or required more time for completion in response to PAF and thrombin. No ultrastructural abnormalities were observed in transmission electron micrographs. Dense granule release of ATP in response to PAF was normal. Thrombin-induced aggregation was dependent upon external calcium concentration in normal but not affected animals. Clot retraction in the blood from affected animals was abnormal. The data implicate a defect of Ca++ mobilization or utilization.
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PMID:A primary platelet disorder of consanguineous simmental cattle. 830 52

Vitamin K is needed to synthesize coagulation factors II (prothrombin), VII, IX, and X through the carboxylation of glutamic acid in vitamin K-dependent proteins which results in the creation of effective calcium binding sites which, in turn, facilitates the coagulation process. Vitamin K exists as naturally occurring vitamin K-I (phylloquinone) in green leafy vegetables and vegetable oils, vitamin K-II (menaquinone) as produced in the gut by bacteroides fragilis and E. coli, and synthetic vitamin K-III (menadoine sodium bisulfite) which is water-soluble and capable of producing serious jaundice in newborns, especially those with instability of glutathione and deficiency of G6PD. Humans require about 5 mcg of vitamin K daily. Since it is indigenously produced in the gut by bacterial flora, dietary deficiency of vitamin K in healthy subjects is rare. Vitamin K is usually the first vitamin given at birth. Newborn babies, however, absorb only approximately 30% of ingested vitamin K, compared to 50-70% in adults. Hemorrhagic disease is a manifestation of vitamin K deficiency in newborn infants. Hemorrhagic disease of the newborn (HDN), early HDN, classical HDN, and late HDN are discussed. The American Academy of Pediatrics recommended in 1961 that all healthy term newborn babies receive 0.5-1.0 mg of vitamin K-I intramuscularly at birth. However, while the authors have not followed those recommendations in their neonatal unit for 15 years, they have experienced only a 0.1% incidence of classical HDN. High-risk newborns at the unit are routinely given the recommended dose of K-I at birth.
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PMID:Vitamin K during infancy: current status and recommendations. 949 99

A 34 year old male bitten by an adult Atheris squamiger snake developed symptoms of nausea, vomiting, diarrhea which were followed by drowsiness and impaired breathing. Local hemorrhage, edema and pain at the bite-site occurred, but no systemic bleeding or hemorrhagic diathesis developed. All clinical and laboratory parameters were in the normal range except for afibrinogenemia, thrombocytopenia and slight proteinuria. Replacement therapy (fibrinogen and platelet concentrates) and treatment of shock stabilized the patient within 2d and coagulation returned to normal. Atheris squamiger venom was subjected to biochemical and biological analysis. The LD50 of the venom was 5 mg/kg (mice, s.c.). It produced local hemorrhage corresponding to about 25% of the activity of puff adder venom (Bitis arietans). In vitro the venom had a fibrinogen-converting activity, it did not activate purified prothrombin but very likely contained a F V and Ca2+-dependent prothrombin activator. The venom exhibited strong platelet-aggregating activity, which was not inhibited by protease inhibitors and by EDTA or EGTA. The venom also aggregated acetylsalicylic acid treated platelets indicating, that the arachidonic acid pathway was not essential for activation. Rat serum rapidly inhibited the platelet-aggregating activity of the venom; human serum, however, had only a partial inhibitory effect. Preliminary experiments showed that platelet-aggregating activity may be separated from fibrinogen-converting activity by anion-exchange chromatography.
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PMID:Severe coagulopathy after a bite of a green bush viper (Atheris squamiger): case report and biochemical analysis of the venom. 972 32

Fibrinogen plays a complex role in hemostasis, thrombosis, and vascular disease. Hyperfibrinogenemia is an independent vascular risk factor and dysfibrinogenemia can provoke thrombosis. Afibrinogenemia is usually responsible for hemorrhagic diathesis, and unexpected ischemic lesions are intriguing. We report the case of an afibrinogenemic patient, who at the age of 30 developed ischemic lesions of the feet related to severe stenosis of the iliac and hypogastric arteries. The biopsy of the iliac artery lesion showed an intense myointimal hyperplasia. We performed standard hemostatic analysis and analyzed the activation markers of platelets and coagulation factors and the kinetics of thrombin generation in the patient and in normal control plasmas treated or not with reptilase. Occlusive arterial lesions were attributed to a disruptive hematoma penetrating the vascular lumen. Thrombin concentration after calcium addition increase markedly in the afibrinogenemic patient and in defibrinated normal plasma, as compared to untreated normal plasma. Thrombin-antithrombin complexes (T-AT) were markedly enhanced while F1+2 prothrombin fragments stayed in the normal range. These results suggested activation of coagulation and in vivo circulating thrombin. Thrombin activates the platelets that secrete growth factors for smooth muscle cells and generate the intimal hyperplasia. Recurrent hemorrhage within the vessel wall might induce injury and local thrombin generation. Thrombin not trapped by the clot is available for platelet activation and smooth muscle cell migration and proliferation. The absence of a protective fibrin cap on the intima might account for intima vulnerability and embolization. Afibrinogenemia appears in this paradoxical situation as a vascular risk factor.
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PMID:Embolized ischemic lesions of toes in an afibrinogenemic patient: possible relevance to in vivo circulating thrombin. 1136 14

Haemorrhagic diathesis develops in chronic renal failure, in which calcium antagonists are used widely as antihypertensive agents. Although calcium antagonists are reported to impair platelet function, it has not been examined whether calcium antagonists alter bleeding time. The present study was conducted to clarify whether calcium antagonists affect bleeding time in chronic renal failure. Patients with chronic renal failure without and with calcium antagonists were enrolled (n = 156), and bleeding time (Ivy's method) as well as blood parameters (BUN, creatinine, platelet counts, and haemoglobin) were compared in patients with normal and prolonged bleeding time. Among patients not taking calcium antagonists (n = 34), three cases manifested prolonged bleeding time, whereas abnormal bleeding time was observed in 31 patients out of 122. Positive correlations were observed between bleeding time and BUN in both calcium antagonist-untreated (r = 0.46) and -treated groups (r = 0.25). The odds ratio for prolongation of bleeding time in patients taking calcium antagonists was 3.52 (95% CI, 1.01-12.33). In 12 calcium antagonist-treated patients with prolonged bleeding time, the withdrawal of calcium antagonists markedly shortened bleeding time (from 11.3 +/- 0.8 to 5.4 +/- 0.8 min, P < 0.05, n = 12). In contrast, in the additional group (n = 9), the continued treatment with calcium antagonists had no effect on bleeding time (from 11.7 +/- 0.9 to 10.0 +/- 1.0 min). Despite the inhibitory effect of calcium antagonists on bleeding time, no clinically serious events associated with haemorrhagic diathesis developed. In conclusion, calcium antagonists prolong bleeding time in patients with chronic renal failure. The subclinical (laboratory) effect of calcium antagonists however is not necessarily associated with haemorrhagic events of clinical significance.
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PMID:Impact of calcium antagonists on bleeding time in patients with chronic renal failure. 1189 10

In our cohort of 555 patients with a total of 1150 vertebral fractures treated with kyphoplasty we performed a 30-day postoperative analysis of cement leakage, neurological symptoms, pulmonary embolism, and infections. In our department, 22% of kyphoplasties were performed with calcium phosphate cement and the remainder with polymethylmethacrylate. All patients were initially assessed by an interdisciplinary kyphoplasty colloquium, composed of consultants in traumatology, radiology, and endocrinology. Indications included fresh traumatic vertebral fractures; painful sintered osteoporotic vertebrae; osteolysis and painful vertebral body collapse caused by multiple myelomas; and lymphomas and pathological fractures due to metastases of malignant tumors (prostate cancer, breast cancer, ovarian cancer, and malignant melanoma) or benign vertebral tumors (hemangioma). Contraindications included patients with instability of the posterior wall and/or pedicles, an infection of the fractured vertebra, a severe hemorrhagic diathesis, known allergies to the cements, pregnancy, and ASA score of 4. The standard postoperative computed tomography scan of the kyphoplasty-treated vertebrae revealed a dorsal cement leakage in 38 vertebrae representing 3.3% of all levels. A permanent monoparesis of the left leg, 2 cases of temporary neurological deficits, 2 cases of hemorrhage, and 1 asymptomatic pulmonary embolism were observed as postoperative complications. We observed no complications relating to polymethylmethacrylate described in the literature. By careful interdisciplinary indication setting and a standardized treatment model, kyphoplasty presents a safe and effective procedure for the treatment of various vertebral fractures.
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PMID:1150 kyphoplasties over 7 years: indications, techniques, and intraoperative complications. 1930 1


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