Immunologic thrombocytopenic purpura Report of a case

ORAL .

MEDICINE .

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IMMUNOLOGIC Report Sheldon

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THROMBOCYTOPENIC

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PURPURA

of a Case Holen, D.D.X.,”

New York,

N. Y.

P

URPURA is a condition characterized clinically

by petechiae or ecchymosis in the skin as well as by hemorrhage from mucous mernbranes and bleeding into various tissues. It is often associated with thrombocytopenia but may also be involved with increased capillary fragility, simultaneously or independently.7 If thromboeytopenia occurs, we can assume that platelet production is decreased or that platelets produced in normal numbers are being destroyed 01 removed from the circulation at a higher rate than normal. Immunologic thrombocytopenia indicates excessive platelet destruction with no significant reduction in platelet formation. It is believed to be a direct action on t,hc platelets produced by a circulatin, 0 antiplatelet agglutinin.” For example, in the case of thrombocytopenia produced by quinidine, administration of a tcsl. dose of the drug after the platelet count had returned to normal produced a precipitous drop in platelets frorn 325,000 per cubic centimeter to 25,000 per cubic centimeter in two hours. Xvcn if a.11platelct production had been corn pletely paralyzed by the quinidinc, it would have taken approximately three: days to reduce the level of circulating platelets t,o such a low figure. C)thc~ often showed :I studies on so-called ‘ ‘ idiopathic ’ ’ tllronlhocytopenie ~)uq~ula powerful antiplatelct agglutinin to hc absorbed by the l~latelets.‘” When normal platelets were transfused to the patient, they rapidly tlisappearcd from his blood, and administration of his plasma to a normal recipient ~a~~secl a striking decrease of the recipient’s circulating platelets.” Ant ibotlies have been demon streted in a patient’s blood for as Ion,(I as six months following cliscontiuuancc of quinidine therapy, even though the thron~boc~tol~erlia had subsided cornplete1y.l’ It is also concluded that altered morphology ot’ the rl~egi~k~~r~o~~~i~~s (probably platelet producers) in the bone marrow is carwtl 1)~ the SHI~Cl;\Tsin or agglutinin which afScct,sthe circulahing platelets.” *Resirilent

in

Oral

Medicine,

Montefiore

Hospital.

929

Agents to which this inrmunologic t hl~on~~)oc~toperlic state can be att,ributed are Sedormid, a sedat,iw no longc~r in vogue: quinidinc, a drug often used j tl t.he t,reatment of auricular fibrillation all(l othc>r cardiac arrhythmias; and quinine. Athrombocytopcnic purpura due to chlorothiazide (Ijiuril, a very popular nonmercurial diuretic) has been reported.” l\n immunologic pabhogencsis acting on the capillary endothelium qualit-atively is suggest,cd.l Quinine, sulfapyridinc, and digitoxin are among the drugs known to cauw wthl~onlhocpto~~enic purpura, although they arc mow often associntcd witjh the t hrombocytopenic I-arirt y. Allergic purpura tine I o a varict\* of L’oods, infections. and drugs has been I’(:ported with good ciwumstantial cvitlcncr. Tllc dr~~g list includes arscnobenzol compounds, sulfonamides, iodides, chrysarobin (employed locally in ringworm, psoriasis. and wzema.), instllin, ant1 nrcwthol.” (1~1 SiClns.--I~cch~nlosin of the oral mucous membranes and bleeding frosty the gingival tissues arouncl tlrc twth arc ~11most~uniformly reported in cases ot thromhocytopenic purpura, wilh a lower incidence in the athrombocytopenic form. The rapid action of tlrc above-stat4 mechanism will cause sudden onwt, of bleeding symptoms. 111 tlic case reported here the 01~1,~symptom when the patient, presented for dental trcatnwnt was profnsc gingivnl bleeding. Attjrmpts to treat 111~condition locall~~ wit hollt, in\.wtigat ing the cause resulted in failuw.

Volun1e 14 Numbs

IMMUNOLOGTC

THROMBOCYTOI’ENI(’

Pl~lil’l~l~h

9:< 1

8

The patient continued to bleed from the to the hospital. Repeated packing failed to spontaneously. By the following day all oral wre no oral petechiac, bullae, or ecchymows. the quinidine therapy. The following record Oct. Oct.

28, 195829, 1958-

10,000 20,000

Oct.

30,

40,000

Oct.

31, 1958-

Nov.

The

patient

was

1955-

mouth for tmelre horns following his admission produce clotting, and thf blood finally clot td bleeding had stopped, ant1 t,wo days later there The only treatment was tliscont illuation of shoxs the rctnrll of tlw platolets:

30,000

3, 1958~-“OO,OOO

dischargtvl

one week

after

the

platelcf

count

had

returned

to normal.

DISCIJSSION

From the effects of varying the initial concent,ration of each component of the complex on the amount of complement fixed, from the kinetic aspects of the sequential reactions, and from other chemical and physical properties of the various components involved, Shulman I1 deduced a steric and kinetic model for the sequence and mechanism of reactions leading to (1) formation of a complex from an antibody, a haptene (quinidine), and a cell membrane (platelets) and (2) fixation of complement by the complex. The results of this study were consistent with the possibilities that. the protein moiety of a haptcnic a,ntigen involved in the development of an antibody which attaches to a cell is not, necessarily a component of the cell and that the ccl1 reacts with the antibody by virtue of having a surface that is favorable for nonspecific adsorption of certain haptene-antibody complexes. Shulman’s conclusion from in viva studies contradicted the direct destruction of the plat,elcts by the antibody. The minimal amount of antibody which attached to the platelets appeared to increase their susceptibility to the usual mechanisms of sequestration. Megakaryocytcs and blood vessels did not appc~ to be affected by the antibody which causes quinidine purpura, and hemorrhagic manifestations of the disease appeared to be consequent to changes in the platelets alone. Attempts to apply this single immunologic mechanism to all cases of idioI)at,liic thrornhoc~to~~eriic purpura that are characlei~ixed b>- a varia.hle clinical (‘ourse with spontaneous remissions and relapses, an inconsistent response to splcnectonly or to the administration of adrenost,eroids and adrellocorticotropic hormone ( A~YJ’ll.), and discrepancies between dcgrce of hemorrhagic manifest.ations and level of circulating platelets and between the severity OT the disease and the presence in vitro of platelet agglutinin shoultl be avoitlcld. The exact mechanisms of megakaryocytcs, platelcts, capillaries, spleen? ant ibodics, and hormones and their interactions in t,he pathogz~liesis of this cliseasc have not yet been fully explained.

Chcmothcrapy is constantly increasing and char@, 0’ with t,hc introduction of new drugs and new therapeutic regimes for existing dr~lgs. Although no drug is without possible side reactions, rclrtain ones are mot’(l l)ron(~ IO cupric

1. Ackroyd, 2. Ilarkham.

J. E’.: Allergic Purpura, Am. .I. Med. 14: 605, 1933. P., and Tocnntins. I,. M.: 0bservations on the Tl~rot1~boc:vto~~enia 1)uc to Y I udl ine Blood 9: 134, ‘1954. -, .: Blood Platelet Anti-scwm, Its Specificity and Role in Experimental l’rud&ion of Purpura, J. Path. Q- Bact. 25: 94, 1952. liolton, F. G., and Dameshek, IV.: Thromboc~yt~openic Purpura Due lo Quinidine. 1. Clinical Studies, Blood 11: 547, 1956. Rolton, F. G.: Thrombocytopcuic Purpura Due to Quinidiuc. IL. Serologic Mechanisms, Blood 11: 547, 1956. Horowitz, H. l., Shapiro, B., and Rubin, 1. L.: htl~rornl~ocytopenic I’urpura (:aused 1,: Chlorothiazide, NCK Tork ,J. Mod. 59: 6, 1939. Miale, J. 13.: Laboratory nledicinc-Hematology, St. Louis, 3958, The C. V. Mosby Cow pSAy. S&en, R. ,T., and Ral)iuovitz, 11.: l’l~ronll)ocytol~enic, I’urpura Due to Quinidine, Drit. M. J. 5111: 20, 1958. Steffen, C.: The Isolation of Platelet Auto-antibodies and Studies ou Passively ‘I’r:~l~h ferable Thrombocptopenia EfYect, Internat. Arch. Allergy 13: ti, 1958. Stefanini, M., Chatteqea, .1. R., and Adelson, E. : Immunologic Aspects of Idiopatlril, Thrombocytopenic Purpur?, 3. Clin. Invest. 31: 665, 1952. Shulman, R. N. : Immunoreactions Involving Platelets, J. Expel. Med. 107: 5, 1958. l’ullic: J. L.: Identification and Significance of Platelet Antibodies, New England .T. hLvl. 255: 541, 1956.

3.Beds2‘2P ’ 4. 3. 6. i. S. 9. 10. 11. 12.

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