Ivy Bleeding Time Research Articles

Ｆｉｌｔｅｒ Ｂｌｅｅｄｉｎｇ Ｔｉｍｅ（ＦＢＴ）による血小板機能の評価

Currently we developed a new in vitro test of hemostasis, the filter bleeding time (FBT), which is based on progressive decrease of flow rate of citrated blood through a disk filter of Woven Dacron under controlled pressure as platelet aggregates occlude the filter. FBT is defined as the time when the blood drop rate has fallen to less than 1/30sec. There was a high correlation (r=-0.91) between FBT and platelet count below 105/μl in dogs made thrombocytopenia by estradiol. There was a significant correlation (r=0.65) between FBT and Ivy Bleeding Time (IBT) in 59 patients referred because of a suspected bleeding disorder. FBT was prolonged in 3 of 3 patients with Glanzmann's thrombasthenia, 5 of 6 with von Willebrand disease and normal in 6 of 6 with hemophilia. FBT was more sensitive than IBT in detecting abnormal platelet aggregation in response to collagen, epinephrine or arachidonate. A monoclonal platelet antibody (HP1-1D), which is a specific antibody for platelet membrane glycoprotein IIb and IIIa, increased FBT in a dose dependent manner. FBT was prolonged by adding 0.1μM prostaglandin I2 and an ADP scavenge system, CP/CPK/ATP but not by adding thromboxane synthetase inhibitor, UK-37, 248 or UK-38, 485. Thromboxane synthetase inhibitors had, however, a synergistic effect on FBT when added with CP/CPK/ATP. Oral ticlopidine 250mg b. i. d. for 7 days increased FBT as well as IBT and Template bleeding time. Additional increase in FBT and skin bleeding times was produced by simultenous taking of 650mg aspirin b. i. d. for 7 days.FBT was significantly shorter in smokers than in non-smokers. It is suggested from these observations that FBT is a useful test of platelet function and has certain advantages over skin bleeding time methods.

EFFECTS OF MANIPULATION OF DIETARY FATTY ACIDS ON CLINICAL MANIFESTATIONS OF RHEUMATOID ARTHRITIS

The effects of manipulation of dietary fatty acids in patients with rheumatoid arthritis were investigated in a 12-week, prospective, double-blind, controlled study. 17 patients took an experimental diet high in polyunsaturated fat and low in saturated fat, with a daily supplement (1·8 g) of eicosapentaenoic acid. 20 patients took a control diet with a lower polyunsaturated to saturated fat ratio and a placebo supplement. Compliance was monitored by plasma lipid gas-chromatographic analysis, Ivy bleeding time, and diet diaries. Results favoured the experimental group at 12 weeks for morning stiffness and number of tender joints. On follow-up evaluation 1-2 months after stopping the diet, the experimental group had deteriorated significantly in patient and physician global evaluation of disease activity, pain assessment, and number of tender joints. The control group had improved in morning stiffness and number of tender joints on follow-up.

Value of the preoperative history as an indicator of hemostatic disorders.

Eighty-three general surgical patients completed the standardized bleeding history questionnaire, and screening tests of platelet counts, prothrombin times, partial thromboplastin times, and Ivy bleeding times were done on these patients. Fifty-two per cent had undergone previous operation; 25% described symptoms of potential hemostatic disorders and seven per cent had positive family histories. Laboratory results indicated abnormalities in five patients (6%). The bleeding history is an important part of the preoperative evaluation of a patient, but it can have serious false-negative results. This history should guide the selection of laboratory tests. Such testing can yield an unexpectedly high rate of abnormalities. When identified, these abnormalities require further investigation.

Clinical evaluation of a new test of hemostasis: The filter bleeding time

The clinical value of a new in vitro test of hemostasis, which we have called Filter Bleeding Time (FBT), was determined in 59 patients referred because of a suspected bleeding disorder. FBT is based on the progressive slowing of the drop rate of citrated blood through a filter of woven Dacron under constant pressure as platelet aggregates occlude the filter. The value for FBT is defined as the time when the blood drop interval has reached 1 minute. The Mayo modification of the Ivy bleeding time (IBT) was performed in all patients; platelet response to ADP, collagen, epinephrine and arachidonate was performed in 24 patients. In 30 normal volunteers FBT measured 1–3 hr after venipuncture was 2.8±1.5 (×-±1SD) min. The FBT was prolonged in 3 of 3 patients with Glanzmann's thrombasthenia, 2 with disseminated intravascular coagulation, 1 with chronic lymphocytic leukemia, 1 with myelofibrosis, and 1 who had taken aspirin. In 6 patients FBT was prolonged while IBT was normal: 4 after taking aspirin, 2 with polycythemia vera. All 6 had reduced platelet aggregation (PA) to ADP (5 μM), collagen (2 mg/ml), epinephrine (5 μM) and/or arachidonate (1.7 μM). In 3 patients FBT was normal while IBT was abnormal: 1 with disseminated intravascular coagulation, 2 undiagnosed; 1 of these 3 had abnormal PA. Of 6 patients with von Willebrand's disease, FBT was prolonged in 5 and borderline in 1; IBT was prolonged in 3, normal in 1, and not done in 2 infants. In 3 patients (1 with myelofibrosis, 1 with collagen disease, 1 with renal insufficiency) IBT could not be determined or was considered invalid due to an abnormality of the skin and/or subcutaneous hematoma; in these patients, FBT and PA were both abnormal. FBT was normal in six patients with hemophilia tested. FBT appears to be highly reproducible and more sensitive than IBT in the detection of disorders of hemostasis involving platelets.

Normalization of fibrin induced platelet aggregation in uraemic patients undergoing haemodialysis

Platelet aggregation in response to ADP, collagen, ristocetin and polymerizing des‐AA fibrin monomers was studied in six patients in chronic, stable, renal failure on maintenance haemodialysis. Fibrin induced aggregation was markedly inhibited prior to but normalized after dialysis. ADP, collagen and ristocetin induced a normal aggregation response both before and after dialysis. The Ivy bleeding time remained prolonged after dialysis.

Symptomatic venous thrombosis of the upper extremity complicating permanent transvenous pacing: Reversal with streptokinase infusion

Symptomatic deep vein thrombosis of the upper extremity is an infrequently recognized complication of temporary or permanent transvenous cardiac pacing. When present, customary treatment includes elevation, rest, and systemic anticoagulation. We report such an occurrence, refractory to conventional management in whom dramatic improvement was observed subsequent to the institution of thrombolytic therapy with streptokinase. A 62-year-old white male factory worker was admitted to hospital with an acute 48-hour history of right arm edema, venous suffusion, and pain. Three months earlier he had undergone elective implantation of a permanent, transvenous silicone-rubber tined bipolar endocardial pacing catheter (Medtronic No. 6962) using the standard cephalic vein approach. There was no history of recent trauma, significant congestive heart failure, or prior documented thromboembolic phenomenon. On admission the patient was afebrile. The right arm was edematous and cyanotic with prominent superficial venous distention over the anterior deltoid area. The circumference of the arm at mid-bicep level was 5 cm greater than the opposite side. The right axilla was tender but without adenopathy. There was no evidence of cellulitis. The pacemaker incision site was unremarkable and pacemaker function was appropriate. An absolute platelet count and leukocyte count on admission were normal as was a prothrombin time of 11 seconds and a partial thromboplastin time of 27 seconds. A venogram of the involved extremity done on admission (Fig. 1, A) demonstrated complete obstruction of the axillary vein at its mid-point (arrows), with clot extending into the right brachiocephalic system and superior vena cava. Heparin therapy was instituted with a loading dose of 5,000 units followed by a continuous infusion of 1,000 unit&r with observed prolongation of the partial thromboplastin time to 55 seconds. In response to a lack of clinical improvement after 24 hours of heparin therapy, thrombolytic therapy with streptokinase was begun. The anticoagulant effect of heparin was reversed with protamine sulfate. A modified Ivy bleeding time, thrombin time, prothrombin time, partial thromboplastin, and fibrin split product level

The effect of prednisone on platelet function tests.

Ivy bleeding time, capillary fragility, threshold ADP concentration for secondary platelet aggregation and platelet adhesiveness were found to be unchanged by 2 d and 6 weeks of treatment with prednisone in 22 consecutive patients with collagen or haematological diseases. Initial high platelet counts were unchanged after 2 d of treatment, but after 6 weeks of treatment the increase was significant. It is concluded that in patients of this category a 6-week treatment with commonly used doses of prednisone does not significantly affect platelet function.

Prolonged bleeding time with adequate platelet count in hospital patients.

100 patients with a modified Ivy bleeding time longer than 10 min in the presence of more than 80 x 10(9)/l blood platelets were studied retrospectively. 72 patients had repeated bleeding times between 10 and 20 min or one or more measurements exceeding 20 min, and were considered to have an unquestionable platelet dysfunction. 39 (54%) of these 72 patients were receiving large doses of antibiotics. Nearly one half of the patients on antibiotics had a bleeding tendency, but most of these patients had additional features that may have interfered with platelet function, or a coagulation defect. In the remaining 33 patients, the prolonged bleeding time was associated with von Willebrand's disease, liver disease, leukaemia/myeloproliferative disease, paraproteinaemia or aspirin ingestion. High doses of penicillin seem to be the most common cause of qualitative platelet disorders in general hospital practice.

The bleeding diathesis in human glycogen storage disease type I: [formula omitted] identification of a naturally occurring inhibitor of ristocetin-induced platelet aggregation

Platelet aggregation in response to adenosine diphosphate (ADP), epinephrine and ristocetin was studied in six patients with glycogen storage disease type I (GSD-I), five of whom had Ivy bleeding times in excess of six minutes. As has been previously reported, these patients demonstrated impaired platelet aggregation in response to ADP and epinephrine. We now report impaired ristocetin dependent platelet aggregation in those patients having an abnormal bleeding time. The impaired platelet aggregation was not corrected by the addition of purified factor VIII/von Willebrand's factor to platelet rich plasma from these patients. Normal ristocetin-induced platelet aggregation was observed when GSD-I platelets were suspended in buffer and factor VIII/von Willebrand's factor was added. Moreover, in the presence of GSD-I serum, the response to ristocetin was normal. When washed platelets from normal subjects were suspended in GSD-I plasma, abnormal ristocetin-induced platelet aggregation was observed. These data indicate the presence of an inhibitor(s) in GSD-I plasma which may be responsible for impaired ristocetin-induced platelet aggregation in patients with glycogen storage disease type I. This conclusion.is further supported by the finding of a parallel inhibition in the binding of 125I-factor VIII/von Willebrand's factor to platelets by various fractions of GSD-I plasma separated by gel filtration. The elution position of the inhibitor and its absence from serum suggest that fibrinogen may be the inhibitor. Plasma from four patients with glycogen storage disease type III showed no evidence of a similar inhibitor(s).

Bleeding time in Uremia: A useful test to assess clinical bleeding

Modified Ivy bleeding time (template) and platelet aggregation to ADP, epinephrine, and collagen were studied in 26 uremic patients who had not recently ingested anti-platelet drugs. Regardless of the aggregating agent used, the abnormalities in platelet aggregation were often mild, even with advanced uremia, and frequently less severe than the effects of common anti-platelet drugs. The inhibition of collagen-induced aggregation was significantly correlated with both increased bleeding time and blood urea nitrogen. Platelet aggregation was not discriminative between clinically bleeding and non-bleeding groups of patients, but the bleeding time was helpful in this regard. In certain cases, the aggregometric patterns differed between drug-induced and uremic thrombocytopathies. Platelet aggregometry appears to be of little help clinically in assessing the severity of the uremic bleeding diathesis.

Correlation between the bleeding time and the platelet aggregating activity of collagen in scoliosis

In 26 patients with scoliosis a significant correlation was found between the platelet aggregating properties of the collagen and the Ivy bleeding time.

Hemostatic Abnormalities in Malignancy, a Prospective Study of One Hundred Eight Patients: Part I. Coagulation Studies

A prospective study of hemostatic abnormalities in 108 cancer patients was undertken at an oncology clinic in a university teaching hospital. Tests included Quick prothrombin time, activated partial thromboplastin time, thrombin time, platelet count, modified Ivy bleeding time, fibrinogen, fibrin degradation products (FDP), euglobulin lysis time, protamine sulfate test, and factor V, VII, VIII and X assays. Ninety-eight per cent of the patients had one or more abnormal coagulation tests. The commonest abnormalities were elevated fibrin degradation products and prolonged thrombin time. Thrombocytosis occurred in 57% of patients, hyperfibrinogenemia in 46%, thrombocytopenia in 11%, and non had hypofibrinogenmia. It is suggested that platelet count, fibrinogen concentration, and serum FDP assay are the most useful tests in assessing the hemostatic abnormalities in cancer patients, although thrombin time, factor V assay, and bleeding time may also be helpful. The peripheral blood smears of 53 patients were reviewed, and only one showed microangiopathic hemolytic anemia. The data illustrate that subclinical coagulopathy is relatively frequent in patients with malignancy.

Template Bleeding Time and Clinical Hemorrhage in Myeloproliferative Disease

In 32 patients with myeloproliferative disorders (MPD), correlations were made among clinical observations of hemorrhagic tendency, template Ivy bleeding time, and platelet aggregation studies. Bleeding time was commonly prolonged, particularly in myelofibrosis. In two cases, this prolongation appeared to reflect a defect in platelet function, which resulted in clinical bleeding. Prolongation of bleeding time did not correlate with degree of thrombocytosis. Two patients with thrombocytosis had serious clinical bleeding at a time when bleeding time was normal. Of the patients, 35% had abnormal findings from aggregation studies, but there was no correlation between aggregation studies and prolongation of bleeding time or clinical hemorrhage. We conclude that bleeding in MPD arises either from a defect in platelet function, which is reflected in a prolonged bleeding time, or from thrombocytosis.

Interaction study between phenprocoumon and flurbiprofen.

The effects of flurbiprofen on various coagulation and haemostasis parameters were studied in 19 patients adequately anticoagulated on a fixed dose of phenprocoumon. Laboratory controls were performed 5 times at weekly intervals. Flurbiprofen 50 mg 3-times daily was given for 2 weeks after an initial control period of 2 weeks. The last control followed 1 week after cessation of flurbiprofen. All changes observed during the administration of flurbiprofen were quantitatively moderate; some reached statistical significance. The prothrombin time (%) Factor II and Factor X values fell; Factor II values remained unchanged. Factor IX values fell only in the first week on flurbiprofen and reached control values thereafter. Phenprocoumon concentration remained constant throughout. There was no change in spontaneous platelet aggregation. Although there was a slight, statistically significant increase in the Ivy bleeding time, it remained within the normal range. These findings suggest that the interference of flurbiprofen with oral anticoagulation is minimal and probably of no clinical relevance.

Delayed hemostatic changes following cardiopulmonary bypass.

A variety of hemostatic abnormalities has been reported in patients following open-heart surgery. Since surgery itself may induce changes in the coagulation system, the analyses of postoperative coagulation assays in the bleeding patients may be extremely difficult to interpret without an understanding of the coagulation dynamics in the nonhemorrhagic postoperative patients. Thus, we studied the pattern of change in several coagulation assays performed on 36 consecutive patients before and during the first two postoperative weeks. Approximately one third of the patients has some clotting abnormality before surgery. Shortened prothrombin time (PT) and activated partial thromboplastin time (APTT) were observed within the first three postoperative days. Only following warfarin therapy (initiated on the third postoperative day) was significant prolongation of PT and APTT observed. During the 14 postoperative days, fibrinogen levels and fibrinogen degradation products progressively increased without prolongation of the thrombin time or decrease in the euglobulin clot lysis time. On the first postoperative day, the platelet count and platelet adhesiveness values were significantly less than before surgery (p less than 0.01 and p less than 0.05). Over the following two weeks, the platelet count and platelet adhesiveness returned to normal. Although there was slight lengthening of the Ivy bleeding time on the first postoperative day, this assay was never abnormal. Thus, we conclude that the following cardiopulmonary bypass there is (1) probably activation of circulating procoagulants, (2) progressive increase in fibrinogen levels, (3) activation to the fibrinolytic system, and (4) transient thrombocytopenia with a superimposed platelet defect.

A Study of the Effects of the Anti-Rheumatic Drug Ibuprofen (Brufen®) on Patients Being Treated with the Oral Anti-Coagulant Phenprocoumon (Marcoumar®)

The effects of ibuprofen on various parameters relating to blood coagulation were studied in nineteen patients adequately anti-coagulated on a fixed dose of phenprocoumon. The patients were studied for a five-week period and they received a fixed dose of phenprocoumon throughout the whole five weeks. Ibuprofen, 200 mg three times daily was added during weeks three and four. The following tests were performed at weekly intervals; Prothrombin time (Quick), Factor II, Factor VII, Factor X, Ivy bleeding time and serum concentration of phenprocoumon. The results showed that in the dosage given, ibuprofen had no significant effect on any of the above tests. It is suggested that the administration of the anti-rheumatic drug, ibuprofen is safe during long-term oral anticoagulation therapy with phenprocoumon.

A Syndrome of Platelet-release Abnormality and Mild Hemophilia

Abstract Two families were studied because of a hemorrhagic tendency. The presumptive diagnosis of von Willebrand’s disease was suggested by low factor VIII levels (7.5%-33%), prolonged template Ivy bleeding time (9.5-17 min), low platelet adhesiveness (0%-8%), normal platelet factor 3, and normal clot retraction. Further studies, however, showed abnormal platelet aggregation with ADP, epinephrine, and collagen, and deficient release of platelet antiheparin activity and 14C serotonin. Patients’ platelets, rendered free of plasma by gel filtration, continued to show abnormal aggregation when resuspended in normal plasma. Plasma from the patients contained greater than 200% factor VIII by immunologic assay. The patients’ coagulant factor VIII level returned to base line within 24 hr after plasma or cryoprecipitate transfusions. Unlike von Willebrand’s disease, management of these patients required both platelets and cryoprecipitate to prevent bleeding.

Osler's disease with impaired adhesion and aggregation of platelets.

Abstract. In the investigation of haemostasis in a 37‐year‐old woman with Osier's disease the Ivy bleeding time proved to be prolonged. Platelet adhesiveness, measured both by Hellem's and Salzman's methods, was decreased and platelet aggregation was clearly reduced after addition of ADP, but only slightly after collagen and epinephrine. Platelet factor 3 activity was normal, as was clot retraction. The therapeutic consequences of the platelet defect, including the risk of using drugs affecting platelet function, are stressed. It is concluded that in cases of Osier's disease the possibility of functional disorders of platelets should be borne in mind.

Bleeding time from incisions standardized by protruding skin fold method.

Summary. A modification of the Ivy bleeding time is described. The incision is made through a protruding skin fold, and constant depth of the incision is ensured by standardizing the amount of protrusion. The method gives reproducible results, within a narrow normal range. Acetylsalicylic acid (ASA) medication approximately doubles the bleeding time with this method. The incisions are only about 3 mm long. The method combines the advantages of the free blood flow of the linear incision methods with the small scar of the punctate methods.

Bleeding time and antiaggregating drugs: A controlled study in elderly patients

The effect of 4 antiaggregating drugs and placebo on standardized Ivy bleeding time was studied in 140 elderly patients. Patients were randomly allocated to treatments and study was carried out using a double blind technique. Tests were performed twice (right and left forearm) in fasting state and repeated 2 hours after drug ingestion. The drugs were 2 compounds containing acetylsalicylic acid at the same dosage (regular aspirin and microencapsulated aspirin) and 2 ergoline derivatives (metergoline and nicergoline). The control bleeding times were normally distributed when plotted on log probability paper with a mean of 162 seconds for males and of 242 seconds for females, the difference being highly significant. Among the drugs tested only acetylsalicylic acid significantly prolonged the bleeding time, the microencapsulated form showing a more marked effect than the regular one. No significant change was observed after the placebo, metergoline or nicergoline.