scholarly journals Observations on the Thrombocytopenia Due to Hypersensitivity to Quinidine

Blood ◽  
1954 ◽  
Vol 9 (2) ◽  
pp. 134-143 ◽  
Author(s):  
PERCY BARKHAM ◽  
LEANDRO M. TOCANTINS

Abstract Studies are reported on a patient who developed thrombocytopenic purpura following quinidine therapy. Quinidine caused lysis of the patient’s platelets in vitro within 40 minutes and complete inhibition of clot retraction. Platelet lysis preceded platelet agglutination. Increasing the concentration of the sodium citrate used as anticoagulant inhibited the in vitro action of the quinidine. No thrombocytolytic effect of the patient’s serum with quinidine could be shown when tested against normal blood. A test dose of quinidine administered orally after the patient had recovered from the thrombocytopenia produced a profound decrease in the number of platelets within 90 minutes, associated with a prolongation of the bleeding time and disappearance of clot retraction. The in vitro hypersensitivity to quinidine persisted for at least four weeks after recovery from the purpura; after six weeks it could no longer be demonstrated.

1979 ◽  
Vol 42 (05) ◽  
pp. 1615-1619 ◽  
Author(s):  
Martin J Smith ◽  
Boyd Braem ◽  
Kent D Davis

SummaryPlatelet acetylcholinesterase (AChE) activity was measured in gel-filtered platelet preparations. Three different anticholinesteratic agents (eserine, neostigmine, and diiso- propylphosphorofluoridate) at final concentrations of 10 μM caused complete inhibition of AChE activity after 30 min incubation at room temperature with either platelet-rich plasma or gel-filtered platelets. Complete inhibition of platelet AChE had no effect on platelet aggregation, factor-3 availability, and plasma clot retraction. We conclude that platelet membrane AChE activity is not required for normal platelet function as measured by these in vitro parameters.


1961 ◽  
Vol 05 (02) ◽  
pp. 304-313
Author(s):  
Sujata Chaudhuri ◽  
J. P Soulier

SummaryUsing normal blood citrated or native, artificial haematocrit levels were obtained in vitro by increasing the relative amount of red cells. Clotting and lytic factors were studied, clot retraction and red cells sediment were measured. Clot retraction was found inversely proportional to the haematocrit level. Red cells sediment and proaccelerin times increased in proportion to the haematocrit level. There was no change in fibrinogen level nor in lytic activity in connection with haematocrit.Thus high red cells sediment found in polycythaemia does not seem to be related to proteolysis but to the incapacity of the fibrin net to retain the excess of cells. The prolonged proaccelerin time is itself not the result of proteolysis but could be an adsorption of factor V on the red cell surface.


1987 ◽  
Author(s):  
J R O'Brien ◽  
M D Etherington ◽  
G P Salmon

A new drug, DN.9693, has low Km phosphodiesterase inhibitory properties. Its effect on seven broad spectrum platelet "function" tests has been compared with the effects of prostacyclin E1 (PGI1) and prostaglandin E (PGE ). The tests were (1) platelet aggregation induced by ADP, collagen, adrenaline, thrombin, arachidonic acid and ristocetin; (2) a new test in which platelets aggregate after adding distilled water to cause osmotic stress; (3) the loss of platelets washed in buffered saline; (4) clot retraction; (5) the glass bead column platelet retention test; (6) the in vitro filter "bleeding time" (see two other submitted abstracts); (7) the amount of platelet factor 4 (PF4) which "leaks" from platelets at room temperature.PGI2 inhibited all seven tests, 50% inhibition of the various tests required from 0.1 to 44ng/ml of PGI2. PGE1 also inhibited in all tests but on average required 18 times higher concentrations. Thus an increase in cAMP may be relevant to all these tests, but an understanding of the mechanisms involved is incomplete. DN.9693 inhibited only the first four tests; the equi-active concentration was about 600 times that of PGI2. DN.9693, 2.5μg/ml, caused 50% inhibition of ristocetin induced aggregation and at 4μg/ml had a minor effect on the filter bleeding time. Thus DN.9693 may affect the platelet membrane glycoproteins. In conclusion it is confirmed that PGE1 is less active than PGI^ but has similar activities. DN.9693 whenstudied in these tests has many, but notall, of the prostaglandin-like properties.


Blood ◽  
1953 ◽  
Vol 8 (1) ◽  
pp. 16-25 ◽  
Author(s):  
ROGER K. LARSON

Abstract A case of thrombocytopenic purpura was studied and evidence of a specific hypersensitivity mechanism was found. The following experimental observations and their conclusions were discussed. 1. A rapid fall in circulating platelets occurred in the patient after a test dose of the drug. This fall was too rapid to be accounted for by inhibition of the bone marrow megakaryocytes alone. 2. Inhibition of clot retraction could be produced in the patient's blood by the addition of minute quantities of quinidine in vitro. This was assumed to demonstrate a specific peripheral action of quinidine on this patient's platelets. 3. No inhibition of clot retraction could be produced by the addition of quinine (an optical isomer of quinidine) to the blood of this patient in vitro. This was further evidence of the marked specificity of the reaction. 4. Complete inhibition of clot retraction could be produced in the blood of a normal individual by the addition of serum from the patient together with quinidine. No inhibition occurred if one or the other was added alone. This was assumed to demonstrate that quinidine did not effect the platelets directly but did so through a combined action with some other element in platelet-free serum. It was felt that this was strong support for an antigen-antibody type of reaction. 5. No significant fall in platelet concentration by the addition of quinidine in vitro could be demonstrated. This was interpreted as evidence against a complete lysis of the platelets as the method of destruction. The disparity between the platelet counts at the end of 2 hours in vivo and in vitro suggested that the platelets were injured in such a manner as to effect their rate of removal by the reticulo-endothelial system and their ability to produce clot retraction.


1965 ◽  
Vol 14 (03/04) ◽  
pp. 361-373 ◽  
Author(s):  
E Gugler ◽  
E. F Lüscher

SummaryPlatelet functions have been studied in relation to hemostasis in two patients with congenital afibrinogenemia.Neither in the plasma nor in the aqueous platelet extracts of these patients was fibrinogen detectable by immunoelectrophoresis or with the aid of the Ouchterlony technique. ADP-induced platelet aggregation, adhesion to connective tissue particles, viscous metamorphosis under the influence of thrombin, clot retraction activity of the platelets, as well as their factor 3 activity were all found normal. Abnormal was the behaviour of the patient’s platelets on glass surfaces : they were unable to adhere to glass and the typical spreading on such surfaces was equally missing. This defect was normalized in vitro by the addition of small amounts of fibrinogen and correspondingly the patients platelets showed normal adhesiveness after fibrinogen transfusions. Normal platelets, suspended in afibrinogénémie plasma lost their adhesiveness toward glass surfaces.After transfusion of Cohn fraction I the prolonged bleeding time of the patients was normal and the clinical improvement presisted for a period of about 3 weeks, this inspite of the fact, that no fibrinogen was detectable by the usual methods 10 days after the transfusion.The significance of these results as well as their implications for the role of fibrinogen in hemostasis are discussed.


Blood ◽  
1979 ◽  
Vol 54 (6) ◽  
pp. 1347-1357 ◽  
Author(s):  
A Kimura ◽  
EJ Bowie ◽  
RJ Campbell ◽  
DN Fass

Abstract Heparinized porcine blood and plasma, at constant hydrostatic pressure, was allowed to flow through a 5-mm incision in a small piece of porcine skin. Changes in the exuded blood volume were measured, and the incision site was examined microscopically. When normal blood flowed through either normal or von Willebrand skin, the exuded blood volume decreased gradually and eventually stopped. Microscopic examination revealed a platelet plug in the incision site. This plug was positive for Willebrand factor when examined by immunofluorescence. In contrast, the blood from von Willebrand pigs continued to flow constantly, and a platelet plug was not seen. The delayed in vitro hemostasis in von Willebrand blood was corrected to the normal range by the addition of either normal plasma or partially purified Willebrand factor. Normal blood, in which the Willebrand factor was immunologically inhibited, showed delayed hemostasis. For this in vitro system, it appeared that plasmatic Willebrand factor played an essential role in hemostasis.


1977 ◽  
Author(s):  
J. Conard ◽  
M. Samama ◽  
B. Vargaftig ◽  
C. Lecrubier ◽  
J. Breton-Gorius ◽  
...  

A thrombocytopathi a associated with a lifelong hemorragic diathesis has been observed in a 18 years old woman. The bleeding time is prolonged. Platelet count and size, and clot retraction are normal. Adrenalin-induced aggregation is abolished and response to ADP and arachidonic acid are impaired. A storage-pool disease is unlikely since platelet ultrastructural aspects appear normal and the number of dense bodies is overnormal, that is confirmed by examination of platelets charged with mepacrine. The uptake of 14(c) serotonin is not increased and it is in correlation with abnormal fluorescence of meracrine-stained dense bodies. Contrasting with aspirin-like syndrome, the first phase aggregation is decreased and in vitro aspirin tolerance test abnormal. Finally, although platelets do not aggregate normally to arachidonic acid, production of Tromboxane A2 and transferable platelet aggregating activity are present. Hence, the thrombocytorathia reported here could not be classified, but a congenital defect is suspected.


Blood ◽  
1946 ◽  
Vol 1 (6) ◽  
pp. 472-496 ◽  
Author(s):  
PAUL M. AGGELER ◽  
JOAN HOWARD ◽  
S. P. LUCIA ◽  
EDITH MILLS

Abstract Determinations of the platelet count, clot retraction, bleeding time, capillary fragility, and coagulation time were made in 64 normal subjects and in 404 patients suffering from various diseases. The normal values for the platelet count done by an experienced technician using the Rees and Ecker method were: mean, 409,000 per cu. mm.; standard deviation, 68,000 per cu. mm.; normal range (M ± 2.σ), 273,000 per cu. mm. to 545,000 per cu. mm. There was a statistically significant relationship between the platelet count and the results of tests of clot retraction, bleeding time, and capillary fragility, but there was no significant relationship between the platelet count and the coagulation time. Factors other than platelet count or platelet function which may influence the results of these tests are discussed. The critical level of the platelet count, below which abnormal bleeding is likely to occur, was found to be approximately 190,000 per cu. mm. in primary thrombocytopenic purpura and 230,000 per cu. mm. in secondary thrombocytopenic purpura. However, platelet counts as low as 100,000 per cu. mm. were found in one patient without abnormal bleeding, and counts as high as 280,000 per cu. mm. were found in another patient with classical primary thrombocytopenic purpura. In all patients in the active phase of bleeding in primary thrombocytopenic purpura and in most with secondary thrombocytopenic purpura, the bleeding time was markedly prolonged and clot retraction was definitely diminished. In approximately one half of the patients suffering from thrombocytopenia without bleeding or from thrombocytopenia complicating other hemorrhagic states, the results of these tests were abnormal. Capillary fragility was increased in approximately three fourths of the patients with primary thrombocytopenic purpura, one half with secondary thrombocytopenic purpura, and less than one half with thrombocytopenia without bleeding or with thrombocytopenia complicating other hemorrhagic states. In the stage of recovery from thrombocytopenic purpura, dissociation of the results of the various tests was sometimes found. In some patients the platelet counts returned to normal hut abnormalities persisted in the tests of the bleeding time, clot retraction, or capillary fragility. In other patients the results of one or all of these tests returned to normal before the platelet count had reached the normal range. These results have been interpreted as evidence of variability in the functional capacity of the platelets.


Blood ◽  
1979 ◽  
Vol 54 (6) ◽  
pp. 1347-1357
Author(s):  
A Kimura ◽  
EJ Bowie ◽  
RJ Campbell ◽  
DN Fass

Heparinized porcine blood and plasma, at constant hydrostatic pressure, was allowed to flow through a 5-mm incision in a small piece of porcine skin. Changes in the exuded blood volume were measured, and the incision site was examined microscopically. When normal blood flowed through either normal or von Willebrand skin, the exuded blood volume decreased gradually and eventually stopped. Microscopic examination revealed a platelet plug in the incision site. This plug was positive for Willebrand factor when examined by immunofluorescence. In contrast, the blood from von Willebrand pigs continued to flow constantly, and a platelet plug was not seen. The delayed in vitro hemostasis in von Willebrand blood was corrected to the normal range by the addition of either normal plasma or partially purified Willebrand factor. Normal blood, in which the Willebrand factor was immunologically inhibited, showed delayed hemostasis. For this in vitro system, it appeared that plasmatic Willebrand factor played an essential role in hemostasis.


1990 ◽  
Vol 64 (01) ◽  
pp. 117-120 ◽  
Author(s):  
Alessandra Casonato ◽  
M Teresa Sartori ◽  
Luigi de Marco ◽  
Antonio Girolami

SummaryWe have investigated the effects of 1-desamino-8-D-arginine vasopressin (DDAVP) infusion on platelet count and bleeding time in 4 patients with type IIB von Willebrand’s disease (vWd). Three of four patients showed a normalization of the bleeding time within 1 h after the infusion, while bleeding time was not modified in the fourth. In accordance with the literature, thrombocytopenia was observed after DDAVP infusion, but this thrombocytopenia was due to the anticoagulants used for blood collection. In two patients (F. I., G. F.) no thrombocytopenia was observed when platelets were counted by fingerstick method but there was a 20% platelet decrease in blood samples collected in sodium citrate and a 50% decrease in samples collected in EDTA. Dramatic falls in platelet counts (70–95%) were observed in the additional two patients (C. A., D.Z.) after DDAVP infusion, when both sodium citrate or EDTA were used as anticoagulants. In the latter two patients there was also a 50% decrease in platelet count when the fingerstick method was used. The decrease in the patient’s platelet count in EDTA samples after DDAVP infusion could be prevented, in part, by the previous additions of an anti GPIb monoclonal antibody and an anti GPIIb-IIIa monoclonal antibody.Thus, the thrombocytopenia observed in the four IIB vWd patients studied after DDAVP infusion seems to be, at least partially, a pseudothrombocytopenia depending on the calcium concentration in the blood samples and the availability of GPIb and GPIIb-IIIa receptors. These findings and the normalization of the bleeding time observed in three of the four patients has led us to reconsider the possible use of DDAVP in the treatment of our IIB vWd patients.


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