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)

We recently described a new case of alpha 1-antithrombin (alpha 1-AT) Pittsburgh, a mutation that transforms alpha 1-AT into a potent inhibitor of thrombin. In contrast to the originally described patient, who had a severe hemorrhagic diathesis, our proband had only a mild bleeding tendency. The current article explores possible mechanisms for the relative hemostatic competence of our patient. The levels of both normal and mutant alpha 1-AT were similar to those of the previously reported case, as was the rise in plasma antithrombin level during an acute phase reaction. The level of protein C, however, was found on several occasions to be approximately 20% of normal. Family studies and examination of the patient's protein C gene on a denaturing gel failed to identify an abnormality. Moreover, the patient's protein C showed no abnormalities suggestive of faulty intracellular processing. However, the protein C in his plasma was for the most part in the activated form and bound to the mutant alpha 1-AT. Thus it is likely that the strong affinity of mutant alpha 1-AT for protein C leads to an increased turnover and thus to a low circulating level. A seeming flaw in that scenario is that the mutant alpha 1-AT also has a very high affinity for thrombin and might be expected therefore to block the activation of protein C. When thrombin was complexed with thrombomodulin (as it is when protein C is physiologically activated at the endothelial surface), mutant alpha 1-AT was far less able to inhibit thrombin than was the case for the free enzyme.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Mechanism of protein C deficiency in a patient with arginine 358 alpha 1-antitrypsin (Pittsburgh mutation): role in the maintenance of hemostatic balance. 770 10

Disseminated intravascular coagulation (DIC) is an extremely rare complication during elective brain tumor surgery. We report the case of a life-threatening intraoperative hemorrhagic diathesis due to a fulminating DIC during the removal of a grade III parietooccipital astrocytoma in a patient with a history of three pulmonary embolisms. Intraoperatively, the patient required 13 U of blood, 9 U of fresh-frozen plasma, and 5.45 L of colloids and crystalloids (total volume infused during the procedure: 12.5 L). Bleeding persisted for 24 h and required further blood component therapy. Laboratory data support the diagnosis of DIC: decreased fibrinogen and platelet count, prolonged thrombin and prothrombin times, and the presence of fibrin monomers. With aggressive and swift treatment of the DIC, the patient survived with transient neurological worsening.
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PMID:Life-threatening hemorrhagic diathesis due to disseminated intravascular coagulation during elective brain tumor surgery. 788 Dec 37

Von Willebrand's disease (vWd) and hemophilia are associated with hemorrhagic diathesis and disturbances in platelet aggregation to vessel wall. We compared the time course of thromboxane A2 (TXA2) formation by platelets during spontaneous clotting of blood of patients with von Willebrand syndrome and from patients with hemophilia A or B with that of healthy controls which were matched for sex, age and serum lipid status. In clotting blood of healthy females the TXA2 production rose at 37 degrees C in 60 min up to 228.2 +/- 32.3 ng/ml. In patients with vWd the TXA2 production at 60 min was significantly lower (129.1 +/- 26.7 ng/ml, p < 0/05). In hemophilia type A and B the TXA2 formation after 5-30 min was significantly diminished in comparison to healthy male controls (p < 0.05). From the diminished amount of TXA2 formed during spontaneous clotting of whole blood we conclude that the activation of platelets of patients with von Willebrand syndrome or hemophilia type A and B is diminished as compared to healthy controls possibly caused by reduced formation of thrombin in the blood coagulation process.
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PMID:von Willebrand's disease and hemophilia are associated with diminished thromboxane A2 (TXA2) formation in clotting whole blood. 814 8

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

DIC is an acquired disorder in which intravascular coagulation may lead to microvascular fibrin formation and a hemorrhagic diathesis. If DIC is acute and severe, fibrin formation may lead to microvascular thrombosis, and consumption of coagulation factors and platelets may result in a hemorrhagic diathesis. Secondary to or simultaneously with coagulation, the fibrinolytic system may be activated, accentuating the bleeding tendency. All the systems involved in DIC, such as coagulation, fibrinolysis, kallikrein-kinin, complement, and possibly other systems are regulated. Coagulation is the central event of DIC. The different coagulation factor derivatives may be generated that can be determined and used as markers for the degree of DIC and for effective control of therapy. Some of the procoagulant and anticoagulant factors are converted in the course of coagulation to their active forms and activation peptides. The active factor is subsequently neutralized by forming a complex with an inhibitor. Hemostatic molecular markers, D-dimer of cross-linked fibrin degradation products (D-dimer), thrombin-antithrombin III complex (TAT), and plasmin-alpha 2-plasmin inhibitor complex (PIC) have all been used for the diagnosis of DIC.
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PMID:[Progress in diagnosis of disseminated intravascular coagulation (DIC)--diagnostic criteria of DIC]. 843 27

Hemorrhagic diathesis and widespread microthrombosis are common in heatstroke. To assess the early stages of coagulopathy in heatstroke, thrombin-antithrombin III (TAT), fibrin monomers, plasmin-alpha 2-antiplasmin (PAP), plasminogen and D-Dimer were measured in 16 heatstroke patients (means +/- SE rectal temperature 42.3 +/- 0.2 degrees C) pre- and postcooling and compared with 8 heatstressed and 23 normal controls. Comparing heatstroke patients with normal controls, TAT, fibrin monomers, PAP and D-Dimer were elevated to (median (range)) 16.5 (4-1000) versus 3.5 (2-7.2) micrograms/l p < 0.001, 16 (4-113) versus 2 (2-9) nM p < 0.001; 3300 (1000-36500) versus 255 (136-462) micrograms/l p < 0.001 and 0.72 (0.22-64.8) versus 0.15 (0.05-0.25) microgram/ml p < 0.01 respectively. Plasminogen decreased to 81% (34-106); PAP, TAT and D-Dimer correlated significantly with hyperthermia (r = 0.577, p = 0.02; r = 0.635, p = 0.01; r = 0.76, p = 0.003). Postcooling PAP decreased to 545 (260-850) micrograms/l p < 0.005, TAT 10 (6-70) micrograms/l, and fibrin monomers 22 (18-86) nM remained unchanged. Heatstressed controls showed mild but significant increase in all markers. Activation of coagulation and fibrinolysis occurs early and is profound and sustained in heatstroke. Cooling seems to attenuate the activation of fibrinolysis only, however, this requires confirmation in a larger study population.
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PMID:Activation of coagulation and fibrinolysis in heatstroke. 897 10

Some platelet alpha-granule contents were assessed in parallel with other markers of hemostatic imbalance in 50 patients with hepatosplenic schistosomiasis (15 patients with compensated hepatosplenomegaly, 15 patients with advanced hepatic fibrosis and ascites and 20 patients during an acute attack of hematemesis from ruptured esophageal varices). Platelet factor 4 (PF4), beta-thromboglobulin (beta-TG), fibronectin (FN), prothrombin fragment 1 + 2, thrombin-antithrombin (TAT) complexes, fibrin degradation products (FbDP) and D-dimer were assessed in schistosomal patients compared to controls (15 healthy subjects). A significant increase in both thrombin (high TAT and prothrombin fragment 1 + 2 levels) and plasmin (high FbDP and D-dimer levels) generation was detected in decompensated patients establishing the presence of a steady state of low-grade disseminated intravascular coagulation, with and without overt bleeding, in these patients. A decrease in plasma FN concentration was found in diseased groups compared to controls. The reduction in plasma levels of FN paralleled the defective liver function and matched the relative decrease in tissue FN in liver specimens of decompensated patients suggesting that FN levels can be used to evaluate the pathological staging of the disease. A significant increase in beta-TG and PF4 levels was noted in decompensated patients with ascites and/or acute hematemesis compared both to controls and compensated patients reflecting platelet alpha-granule release and consequently increased in vivo platelet activation which may initiate and/or perpetuate the pathophysiological mechanisms of the hemostatic imbalance underlying the hemorrhagic diathesis in hepatosplenic schistosomiasis.
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PMID:Fibronectin, platelet factor 4 and beta-thromboglobulin in endemic hepatosplenic schistosomiasis: relation to acute hematemesis. 909 85

By virtue of a severely prolonged aPTT with a normal thromboplastin time (prothrombin time) and a normal thrombin time, severe FXII deficiency has been diagnosed in a woman without a bleeding diathesis or a history of thromboembolic complications. A deficiency of a factor of the contact activation system (FXII, prekallikrein, high molecular weight kininogen) is usually diagnosed during routine coagulation tests demonstrating a prolonged aPTT. The severe and partial deficiency of FXII, of prekallikrein or high molecular weight kininogen is not associated with a bleeding tendency. In contrast, severely factor XI deficient subjects may suffer from a mild hemorrhagic diathesis, whereas FVIII deficiency (hemophilia A, autoimmune "hemophilia", von Willebrand disease) and FIX deficiency (hemophilia B) are associated with a bleeding tendency of varying severity, depending on the clotting activity of FVIII or FIX, respectively. An isolated prolongation of the aPTT due to a lupus anticoagulant, however, is frequently associated with arterial and/or venous thrombosis. Therefore, in case of a prolongation of the aPTT, its cause has to be determined.
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PMID:[A patient with isolated prolongation of aPTT without hemorrhagic diathesis anamnesis: severe, hereditary factor XII deficiency]. 1051 21

The recent observation of increased thrombogenesis in chronic renal failure suggest a pathogenetic role of thrombin in hemorrhagic diathesis of chronic renal failure that may link two paradoxical aspects of this diathesis: hemorrhage and thrombosis. Not only: the accelerated atherosclerosis in uremic patient is also underlined. The possibility of thrombin therapeutic inhibition is then discussed.
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PMID:[Uremic coagulopathy. Role of thrombin]. 1108 63

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


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