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

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

Diagnosing Bernard-Soulier syndrome (BSS), a congenital hemorrhagic disorder of blood platelets, is complicated by the difficulty of separating the giant platelets from other blood cells to allow studies of platelet function and structure. We report on the use of three whole blood assays for diagnosing BSS. Whole blood platelet aggregation responses studied with an electrical impedance aggregometer were equivalent to those more laboriously obtained by using platelet-rich plasma prepared by unit gravity sedimentation and studied with an optical light transmittance aggregometer. Platelet aggregation responses were normal with adenosine diphosphate or collagen stimulation but absent with ristocetin or bovine plasma stimulation. Whole blood radioimmunoassay of platelet glycoprotein (GP) expression was performed by using iodinated murine monoclonal antibodies HP1-1D (anti-GP IIb/IIIa) and 6D1 (anti-GP Ib). After incubation with citrated whole blood, centrifugation was used to separate cell-bound antibody that was quantitated with a gamma counter. The patient's whole blood had a normal level of cell-bound GP IIb/IIIa but a substantially reduced level of cell-bound GP Ib (5% of normal mean). Whole blood smear immunocytochemical staining with monoclonal antibodies and qualitative analysis by light microscopy revealed a considerable reduction of GP Ib expression by the patient's giant platelets, whereas GP IIb/IIIa expression was normal. These data helped establish the diagnosis of BSS. We conclude that these three relatively simple assays of platelets in whole blood should be of particular value in the clinical laboratory differential diagnosis of patients with congenital thrombocytopenias and giant platelet syndromes.
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PMID:Bernard-Soulier syndrome: whole blood diagnostic assays of platelets. 272 65

An otherwise healthy woman developed a hemorrhagic diathesis with fluctuating clinical symptoms and laboratory findings, but without thrombocytopenia, over 8 years. In periods of bad clinical condition, a platelet defect, characteristic of thrombasthenia, was found. In contrast to classic thrombasthenia, electrophoresis of the patient's platelet membranes revealed normal amounts of glycoproteins IIb alpha, IIb beta, and IIIa in the normal positions. Monoclonal antibodies, specific for GPIIIa and GPIIb/IIIa, respectively, bound normally to the P1A1-positive platelets from the patient. Although no antibody and no platelet function inhibitor were evident in the autologous plasma, an IgG1 antibody that was bound to the patient's platelets and was directed against GPIIb/IIIa could be demonstrated. After elution from the patient's platelets, this antibody immunoprecipitated GPIIb (both subunits), IIIa, and a 200-kilodalton (kd) band (probably undissociated GPIIb/IIIa complex) from solubilized normal platelets, but did not react with thrombasthenic platelets. Adding the eluate from the patient's platelets to normal platelet-rich plasma immediately caused concentration-dependent inhibition of adenosine diphosphate (ADP)-induced and collagen-induced aggregation and also strong inhibition of ADP-stimulated fibrinogen binding. Because it was very unlikely from the patient's medical history that the antibody was caused by alloimmunization, the hemorrhagic diathesis must be interpreted as acquired thrombasthenia due to an anti-GPIIb/IIIa autoantibody.
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PMID:Acquired thrombasthenia due to GPIIb/IIIa-specific platelet autoantibodies. 301 87

Bleeding time measurement and investigation of platelet aggregation in platelet rich plasma (PRP) are routine procedures for the diagnosis of defects in primary hemostasis. These tests are subject to methodological difficulties and should be well standardized in each individual laboratory. - In the present study, bleeding time was measured using the Simplate II device in 40 normal subjects. Furthermore, platelet aggregation in PRP induced by ADP, collagen, arachidonate, and ristocetin was examined. 26 patients referred for investigation of a suspected mild bleeding disorder, who had a normal plasmatic coagulation profile, a normal von Willebrand factor activity, and a normal platelet count, were similarly studied. - Based on the reference values established in the 40 normal subjects, platelet aggregation was found to be pathologic in 7 patients and normal in 12. In 7 patients platelet aggregation was considered to be borderline-pathologic as defined by the range of platelet aggregability found in the 10% of our normal subjects showing the weakest aggregation responses. Bleeding time was prolonged in only 3 patients whereas it was normal in the remaining 23. There was strong evidence of a hemostatic defect as assessed by systematic patient history in 6 out of 7 patients with pathologic platelet aggregation, but in only 3 out of 19 showing normal or borderline-pathologic aggregation. - Pathologic platelet aggregation, therefore, represents not only an abnormal laboratory finding but is likely to be associated with a hemorrhagic diathesis. Platelet aggregation studies do not permit etiologic diagnosis of the thrombocytopathy except for the well-defined membrane glycoprotein deficiencies. The bleeding time appeared to be of low sensitivity for the diagnosis of mild platelet dysfunction.
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PMID:[Measurement of bleeding time and study of thrombocyte aggregation. Standardization of methods, normal values and results in patients with suspected hemorrhagic diathesis]. 323 91


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