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)

Hemorrhagic diathesis was observed in patients with renal insufficiency after carbenicillin at serum levels greater than 300 mug/ml. Normal coagulation factors (F. I, II, V, VII, VIII, X), normal PTT, normal platelet counts, negative ethanol gelation test (fibrin monomers) were found as well as a prolongation of thromboplastin time (Quick), thrombin time, reptilase time and thrombin coagulase time. Platelet function was disturbed. In addition, the plasmatic system was involved: inhibition of fibrinogen-fibrin conversion (Belitser assay) and enhanced antithrombin III activity; in vivo the latter was ascribed to a heparin-like activity. In vitro, abnormal III was seen: however an enhanced antithrombin III activity in vitro was not found with carbenicillin and various penicillin derivatives. This study demonstrates that carbenicillin, in addition to its known effect on platelet function, also disturbs the plasmatic coagulation system. This additional effect of carbenicillin is clinically important since protamin chloride effectively blocks bleeding without interfering with antibacterial activity. Both penicillin and penicillin derivatives have been shown to interfere with hemostasis and to cause clinically manifest hemorrhagic diathesis (Fleming and Fish 1947, Lurie et al. 1970a, b, McClure et al. 1970, Yudis et al. 1972, Demos 1971, Waisbren et al. 1971). Carbenicillin interferes with ADP-, collagen- or thrombin-induced platelet aggregation and with the release reaction both in vivo (McClure et al. 1970, Cazenae et al. 1973) and in vitro (McClure et al. 1970, Cazenave et al. 1973). In addition Lurie and colleagues (1970b) concluded that an inhibition of the conversion of fibrinogen to fibrin is involved although no experimental details were given. Later Brown and colleagues (1974) concluded that carbenicillin at usual dose levels "only affects the platelet component of hemostasis and has little effect on fibrin formation or other phases of coagulation in patients with normal renal function".
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PMID:Bleeding in uremic patients after carbenicillin. 103

After a bite by the aglyphous red-necked keelback snake Rhabdophis subminiatus a complete defibrinogenation syndrome with severe hemorrhagic diathesis developed in a 25-year-old man. In vitro studies showed that the venom gland extract of the snake contains a very active prothrombin (Factor II) activator. The thrombin generated is inhibited neither by antithrombin III nor the antithrombin-III-heparin complex. The venom gland extract stimulated also the tissue plasminogen activator; however, it did not cause direct activation of plasminogen, protein C, Factor X or direct degradation of fibrinogen.
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PMID:Hemostatic changes due to the venom gland extract of the red-necked keelback snake (Rhabdophis subminiatus). 180 26

The levels of alpha-2-antiplasmin (alpha 2-AP), antithrombin III (At III) and plasminogen were studied in 21 patients with acute nonlymphoblastic leukemia (ANLL) before and after induction chemotherapy and during bone marrow cellularity recovery after the postchemotherapy aplastic phase. In the patients with M2, M3 or M4 leukemia who had clinical and laboratory evidence of DIC, the alpha 2-AP levels were very low in the initial phase of the disease but improved significantly during recovery of marrow cellularity. At III and plasminogen values were in the normal range at disease onset and showed no significant modification during the course of leukemia. Proteolytic cleavage of alpha 2-AP by granulocyte proteases, rather than hyperfibrinolysis, may be responsible for the low levels of the inhibitor in the proliferative phase of ANLL. This alpha 2-AP deficiency may well contribute to hemorrhagic diathesis in ANLL independently of the presence or absence of hyperfibrinolysis or DIC. Moreover, the lower alpha 2-AP levels observed during the proliferative phase of ANLL may relate to disease activity.
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PMID:Alpha-2 antiplasmin in acute nonlymphoblastic leukemia. 246 77

This study concerns a case of congenital homozygous deficiency in alpha 2-antiplasmin associated with a severe hemorrhagic diathesis. Heterozygous family members also show a mild bleeding tendency. The propositus is a 17-yr-old male born of white parents and showing a severe hemorrhagic diathesis characterized by spontaneous bleeding in the joints since his early childhood. He was originally suspected of having factor XIII deficiency but was found to have normal functions of the coagulation system and the platelets. Except for alpha 2-antiplasmin, all protease inhibitors showed normal plasma values. With the immediate plasmin inhibition test (synthetic substrate), only 2% of normal functional inhibition was detected, while no reaction with monospecific antisera for alpha 2-antiplasmin was observed. Inhibition of activator-induced fibrinolysis in vitro was reduced. No enhanced spontaneous in vitro fibrinolysis was detected nor were there signs of increased in vivo fibrinolysis during an asymptomatic period. During recovery from a hemorrhagic episode, signs of previous consumption of antithrombin III, alpha 2-macroglobulin, factor XIII, and inter-alpha-trypsin inhibitor were noted. After the diagnosis was made, treatment with tranexamic acid (4 daily doses of 1 g) was effective for about 2 yr. Among the 37 family members studied, a separate group of 16 individuals (including the father and mother of the propositus) with approximately one-half normal plasma levels of alpha 2-antiplasmin both functionally (59% +/- 6%) and immunologically 48% +/- 8%) was discovered. The defect appeared to be inherited as an autosomal recessive gene; no ancestral consanguinity could be shown. The group of apparent heterozygotes as a whole showed increased levels of alpha 1-antitrypsin (142% +/- 39%; p less than 0.01), indicating systemic consequences of the deficiency and reduced binding (+/- 50%) of alpha 2-antiplasmin to fibrin. Six exhibited a mild hemorrhagic diathesis for which no explanation was provided by routine screening of coagulation and platelet functions; also, within the group of heterozygotes, the occurrence of the bleeding tendency did not correlate with differences in residual alpha 2-antiplasmin levels and functions. It is concluded that not only the absence of alpha 2-antiplasmin but also a reduction in its plasma level to +/- 60% of normal may predispose to a hemorrhagic diathesis.
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PMID:A familial hemorrhagic diathesis in a Dutch family: an inherited deficiency of alpha 2-antiplasmin. 617 59

Hemostasis was studied in 55 patients with myeloma, grouped in three groups according to the clinical stage of the disease. Thrombocytic adhesion, aggregation, activity of TF3 and TF4, of antithrombin III, FMDC level, FDP titre and fibrinolysis test were determined on the background of the screening coagulation tests. The studies were carried out before the treatment and were followed up after the therapeutic response or in the absence of improvement. Thirty per cent of the patients had manifestations of hemorrhagic diathesis, and 5 per cent - thromboembolism. Essential hemostatic deviations were found: progressive thrombocytopenia and thrombopathia and DIC syndrome that correlate with the stage of the disease, being most severe among the stage III patients. The patients that responded to the treatment had a great part of the hemostatic disorders corrected, and in case of no effect from the treatment - the deviations persisted, intensified and in 5 of the patients were responsible for the fatal end. The pathogenesis of the hemostatic deviations is complex and is associated with the characteristics of the basic disease and the concomitant complications.
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PMID:[Proceedings of the 7th Congress of Internal Medicine]. 665 83

Collaborative studies on hemostasis in dengue hemorrhagic fever (DHF) patients by Indonesian and Japanese teams revealed that all DHF patients had manifestations of the acute type of disseminated intravascular coagulation (DIC). Prolongations of activated partial thromboplastin time and prothrombin time and decreases of platelet counts, fibrinogen, prothrombin, factor VIII, plasminogen and antithrombin III activities were observed transiently during the acute stage of DHF. It was also found that alpha 2 antiplasmin was decreased in the acute stage to 32% of the normal level on the average. This may characterize the hemorrhagic diathesis of the DHF patients.
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PMID:Features of DIC in dengue hemorrhagic fever. 666 46

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

Clot formation is the final result of interaction among multiple plasma proteins; after activation, it results in the conversion of fibrinogen to fibrin and cross-linking of fibrin by activated factor XIII, which stabilizes the formed clot. Deficiency or functional abnormality of the factors involved in these reactions causes bleeding disorders. Natural inhibitors of clotting factors include antithrombin III, protein S, and protein C. When activated, these proteins inactivate specific clotting factors, providing a regulatory mechanism that serves to control the coagulation response and limit the extension of the clot. Physiologic or natural inhibitors should not be confused with acquired inhibitors of coagulation factors, which are discussed in this review. Inhibitors to coagulation factors, also known as circulating anticoagulants, are antibodies that neutralize specific clotting proteins, thereby interfering with their normal function. Antibodies may be directed against isolated clotting factors, as is the case with factor VIII or IX inhibitors. On the other hand, the antiphospholipid antibodies are known to develop against multiple coagulation proteins. In contrast to patients with antibodies against isolated clotting factors, who commonly present with spontaneous bleeding, individuals with antiphospholipid antibodies may be asymptomatic or present with venous or arterial thrombosis. In this article I refer to inhibitors developing in patients with hemophilia A or other congenital factor deficiency as alloantibodies, and to spontaneous formation of antibodies in patients without prior history of hemorrhagic diathesis as autoantibodies. The antiphospholipid antibodies are discussed separately.
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PMID:Inhibitors to clotting factors. 932 77

We report the result of a randomized, controlled, open trial of anti-thrombin therapy for herpes zoster-associated pain. Fifty-five herpes zoster patients within 8 days after the onset of skin lesion were enrolled in the trial. Patients were treated with an optimal dose of oral acyclovir (4000 mg/day for 7 days) with or without intravenous administration of a specific anti-thrombin agent, argatroban (10 mg/day, three times a week). Administration of argatroban reduced pain intensity at the 4th through 21st day after the initiation of treatment as determined by visual analogue scale (Mann-Whitney U test, p < 0.05). It also shortened the median time to cessation of analgesic use (14 days vs. 24 days, p = 0.02, logrank test), although it did not significantly reduce the median time to cessation of pain (21 days vs. 43 days, p = 0.07, logrank test). None of the enrolled patients showed evidence of adverse effects including hemorrhagic diathesis. The results suggested that relatively low doses of argatroban are effective in reducing herpes zoster-associated pain. Up-regulation of prothrombin expression by the vascular endothelial and sweat gland epithelial cells in the active skin lesion and transient elevation of plasma thrombin-antithrombin III complex levels in a proportion of patients suggest a lesional generation of thrombin in herpes zoster. This may be relevant to the beneficial effects of the anti-thrombin treatment on the resolution of herpes zoster-associated pain.
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PMID:A specific thrombin inhibitor, argatroban, alleviates herpes zoster-associated pain. 1144 71


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