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)

The administration of mithramycin to patients with testicular tumors has been accompanied by a hemorrhagic diasthesis, often in the absence of thrombocytopenia. Bleeding time, platelet aggregation, platelet adenine nucleotide levels, and coagulation factor assays were studied in three patients receiving mithramycin for embryonal testicular carcinomas. These studies demonstrated a drug dependent, reversible hemorrhagic diathesis associated with (1) prolongation of bleeding time, (2) decreased platelet aggregation responses to ADP, collagen, and epinephrine, and (3) depleted platelet stores of ADP in the absence of thrombocytopenia. These abnormalities were temporally correlated with the onset of mucocutaneous bleeding in all patients.
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PMID:Acquired platelet dysfunction following mithramycin therapy. 14 32

The platelet function was studied in 23 patients with systemic lupus erythematosus, all of whom met the diagnostic creteria established by the American Rheumatism Association. They were not under any treatment, especially with any drug that might interfere with platelet function. The same study was performed on a control group composed of volunteers donors at a blood bank. The platelet count was definitely lower in the patients with lupus than in the control subjects (p less than 0.0005), although a clear thrombopenia was observed in only two indivduals (8.7 percent). Anti-platelet antibodies were found in only six cases (26 percent). There was a linear correlation between thrombopenia and the presence of hemorrhagic diathesis and low levels of C4 and CH50 components. Plateler adhesiveness was clearly lower in the lupus group than in the control group (p less than 0.0005). The presence of kidney disease determined a greater impairment of the platelet adhesiveness (p less than 0.0025). A notable defect on platelet aggregation was induced by ADP, adrenaline and collagen. This was more apparent in the group of patients exhibiting a higher degree of clinical activity and in those who showed a serum complement decrease. The mechanism responsible for this thrombopathy appears to be an interference in the platelet function due to the presence of circulating immunocomplexes. They adhere to the platelet membrane blocking its function and inhibiting the release of the necessary thrombocytic components for the second phase of the aggregation. This platelet alteration is not usually manifested clinically; for this reason no relationship was found between this platelet defect and the presence of hemorrhagic symptoms in our patients. The condition is reversible and may disappear after therapy with steroids and/or immunosuppresive agents.
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PMID:[Platelet function in systemic lupus erythematosus (author's transl)]. 45 1

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

Methylhistidines are among the amino acids which are present in increased concentrations in the plasma of severely uremic patients who may have a hemorrhagic diathesis. Histidine contains an imidazole ring, and our previous work has shown inhibition of collagen-induced platelet aggregation by imidazole in concentrations as low as 0.5 mM. Collagen-induced, adenosine diphosphate-induced, and norepinephrine-induced platelet aggregation were tested in platelet-rich plasma by a turbidimetric technique after incubation of the plasma with varying concentrations of the methylhistidines for 1 hour. Platelet aggregation was unaffected by methylhistidine concentrations up to 0.6 mM. Only norepinephrine-induced platelet aggregation was slightly inhibited at a concentration of 4.7 (mM far higher than found in uremic patients). The imidazole ring as a portion of the methylhistidine molecule appears to have lost much of its effect on platelet aggregation.
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PMID:Failure of methylhistidines to inhibit platelet aggregation at concentrations found in uremic plasma. 114 54

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

A 64-year-old woman with a 15-years-history of rheumatoid arthritis developed generalized hemorrhagic diathesis. Routine coagulation tests revealed a slightly diminished platelet count only. Platelet aggregation in vitro induced by ADP, collagen, thrombin, arachidonic acid and ristocetin were reduced. The patient's plasma aggregating activity was significantly diminished which was due to a decrease of the intraplatelet nucleotide pool. The number of mepacrine labelled bodies as well as dense bodies in electron microscopy was below the normal values as well. Moreover, the intraplatelet concentration of cyclooxygenase--malonylodialdehyde (MDA) and lipoxygenase pathway products were lowered. Total platelet immunoglobulin G and M contents were significantly increased. The platelet survival time (in vitro aspirin method) was slightly shortened. Finally the diagnosis of delta-acquired platelet storage pool deficiency (delta-SPD) was established and possibilities of treatment were discussed.
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PMID:[Acquired platelet storage pool deficiency in rheumatoid arthritis]. 178 43

Platelets from a patient with an acquired hemorrhagic disorder had a severely impaired response to collagen, whereas platelet aggregation to other agonists and coagulations tests were normal. No abnormalities of the patient's platelet membrane glycoproteins (GP) were seen. Treatment of the patient with immunosuppressive agents temporarily improved both the bleeding tendency and the collagen responsiveness of the platelets. An IgG was found to be present in the plasma, directed against a protein comigrating with GPIa, and coadsorbing with GPIa to insoluble collagen fibers in a Mg2+(-)dependent manner. Furthermore, GPIa was recognized by the patient's antibody when affinity-purified GPIa-IIa was used as antigen. Finally, the GPIa-IIa complex was immunoprecipitated from a platelet lysate by patient's plasma. In addition, purified platelet specific IgG's from the patient inhibited aggregation of normal platelets induced by collagen or by wheat germ agglutinin. We conclude that the lack of response to collagen of the patient's platelets may well be due to the presence of an autoantibody against GPIa.
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PMID:Lack of platelet response to collagen associated with an autoantibody against glycoprotein Ia: a novel cause of acquired qualitative platelet dysfunction. 227 30

Partial resection of the liver is the only curative treatment for patients with hepatocellular carcinoma associated with severe cirrhosis of the liver. Surgical hemostasis on the cut surface of the cirrhotic liver appears very difficult because of the resultant deep cavity and the marked hemorrhagic diathesis. However, by using the microcrystalline collagen powder and the fibrinogen tissue adhesive, complete hemostasis and prevention of postoperative bleeding can be obtained, with minimal blood loss and hepatic ischemia.
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PMID:Use of microcrystalline collagen powder and fibrinogen tissue adhesive for hemostasis and prevention of rebleeding in patients with hepatocellular carcinoma associated with cirrhosis of the liver. 246 32

Platelet function profiles were studied in 3 patients with megakaryoblastic leukemia. All patients had a moderate decrease in platelet counts with abnormal platelet retention. One patient who developed hemorrhagic diathesis had prolonged bleeding time. In all patients platelet aggregation was defective after the addition of ADP, collagen, adrenaline, or U46619, a thromboxane A2 agonist. Malondialdehyde was reduced in all patients, as was platelet serotonin. Plasma beta-thromboglobulin levels were normal in all cases whereas PF4 was markedly elevated in one. Platelet dysfunction was not reversed by clinical remission. These studies confirm that megakaryoblastic leukemia is associated with a thrombocytopathy which may play a role in hemorrhagic diathesis and should be taken into account in the management of these patients.
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PMID:Platelet dysfunction in acute megakaryoblastic leukemia. 252 6

Daunomycin (rubidomycin, daunorubicin), an anthracycline antimetabolite used in the therapy of acute leukemia, is highly toxic to both normal and malignant cells. Treatment with daunomycin may produce thrombocytopenia and bleeding which have been attributed to bone marrow toxicity. We have examined daunomycin to determine if a direct drug effect on platelet structure and function could contribute to a hemorrhagic diathesis in some patients on therapy. Normal citrated platelet-rich plasma was reacted in vitro with daunomycin and/or collagen with structural assessment by phase and electron microscopy and functional studies by platelet aggregation, [2-14C]5-hydroxytryptamine release studies and assays for released cytoplasmic marker enzyme, lactic dehydrogenase, in the supernatant fluid. High [greater than 0.04 mg/ml (greater than 0.07 mM)] concentrations of daunomycin were associated with structural changes, specifically by platelet swelling, vacuole formation and mitochondrial swelling with interruption of the trilaminar membrane. Platelets, exposed to low doses of daunomycin, 0.001 to 0.01 mg/ml (0.00177-0.0177 mM) of platelet-rich plasma, were dysfunctional with decreased aggregation with collagen and decreased [2-14C]5-hydroxytryptamine release. These studies indicate that daunomycin has a direct effect on platelets in vitro which may explain certain instances of bleeding observed in some patients undergoing therapy.
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PMID:The effect of daunomycin on platelets in vitro. 261 25


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