Control of hemorrhage—or transfusion

Control

of Hemorrhage-or MORRIS

JOSEPH,

M.D., Passaic,

Transfusion New JersqL-

ease of the newborn and certain liver and gallbladder disease with increased prothrombin time. Vitamin K cannot be immediately effective because it has to be converted by the liver to prothrombin before results can be obtained. NearI)fifteen years ago a preparation appeared Ivhich represented an old foIkIore remedy for bleeding, nameIy, the extract from shepherd’s-purse. Other plants such as wood sorrel, rhubarb oxalis, etc., had been tried empirically for the control of bleeding. In the extract of shepherd’s_purse Steinberg and the active principles as Brown’O identified certain dicarboxylic acids (e.g., oxalic and malonic). This resuIted in the cIinicaIIy usefu1 scientific preparation caIIed koagamin.@ At first koagamin was used as a therapeutic agent for conditions causing genera1 oozing in a nound. More recently, however, koagamin has become, in addition, an exceIIent prophyIactic hemostatic agent especiaIIv in the rhinoIaryngoIogic field where tonsrIIectomies are so frequent. The efEcacy of this drug is even more striking where hemorrhagic tendencies are known to exist. Our clinical experience with this preparation is in accord lvith the results reported in the Iiterature during the past fifteen years. The foIlowing pubIished reports covering a wide range of conditions emphasize this fact: General surgery: thyroidectomy,’ g gastrointestinal,g,21 cholecystectomy for obstructive jaundice,g appendectomy,?’ partia1 mastectomy,2L prostatic resection,“,” prostatectomy..6 Ophthalmology and otorhinolaryngolog~~: Eplstaxis,R.7CY.?l pre- and post-tonsiIIectomres,8 9.?1 pre- and postadenoidectomies,x,21 radical antrum operations (CaIdweII-Luc), rhinophyma and other plastic surgery,23 orbita bIeeding.2’ Obstetrics and gynecology: Uterine bIeedhemorrhagic fibromas,I* ing, g.18,21menorrhagia,g postpartum hemorrhages,18,21 peIvic enucleations,‘* placenta previa,lg vagina1 hysterectomy,’ cholecystectomy,’ melena neonatorum.lR

time immemorial, bleeding has been matter of great concern to the victim as well as to the physician. Superficial bleeding or an ordinary nosebIeed in normal individuals may not be a cause of concern. However, these same simple types of hemorrhage in a patient with bIeeding tendencies change the picture compIetely. A simpIe tooth extraction, a minor cut, a routine tonsillectomy or epistaxis may be folIowed by grave consequences and often requires heroic control measures. Before the da,ys of abundant transfusions and blood banks death was not uncommon in these minor a&dents and procedures. Even at this late date such types of blood loss may stil1 be fatal in remote parts of this country, to say nothing about the more remote parts of the world. There are times when absence of the rarer bIood types makes hemorrhage a real hazard. This is particuIarIy true in hemophiIiac tendencies where time is of the essence. Then again, in medical centers with our most modern facilities, at times the demand for blood in genera1 surgery is greater than the supply. In fact the ease with which blood can be obtained often defeats the rea1 object of the blood bank. Patients are often hastened to surgery without proper buiIding up, even when no emergency exists. This tends to exhaust bIood banks needIessIy. Surgeons should begin to consider this phase more seriously so as to avoid what occasionalI; appears like an alarming situation. This condition makes one wonder if it is not wise to prevent bIood loss as much as possibIe and abolish this feeling of complacency and security induced by the existence of blood banks. Until a few years ago the tourniquet or actual Iigation of bleeding vesseIs was the most potent means of controIling hemorrhage. More recentIy vitamin K was introduced. This substance, however, is primariIy of vaIue in reducing clotting time in hypoprothrombinemia accompanying jaundice, hemorrhagic disROM

Fa

905

ControI

of Hemorrhage

Urology: BIeeding bIadder,“r transurethral prostatic resection,‘” hematuria,Y,r2 transurethra1 prostatectomy.4 Internal medicine: BIeeding peptic u1cers,g hemoptysis,1r,21 hematuria of various etioIogies,g hemophilia,’ L~g~12~21 toxic thrombocytopenic

PROTHROMBI N

+

(held neutml by antipmthrombin)

EssentiaIIy the diagram devised by Howell many years ago has never been materiatly altered. It is believed that koagamin has a tendency to separate the calcium ions from the prothrombin, thus permitting the latter to act more quickIy. (Fig. I.)

THROMBOPLASTIN

+

(released by dirlntegmtion

CALCIUM

IONS

(always present in

of plotelets)

normal blood)

FIG. I. Clotting mechanism of bIood according to MowelI.

purpura,21 hemorrhagic purpura,5,21 hemorrhage associated with jaundice,21 Ieukemiael and chronic osteomyeIitis2r AIthough we have observed no untoward effects, it would seem wise to exercise caution in vascular diseases showing thrombotic tendencies. In our own series extending back eleven years we have had no such compIication, and search of the Iiterature reveals that no case of thrombosis has been reported with koagamin. ADMINISTRATION

In spite of its innocuousness, practica1 appIication in its use has shown that any initia1 dosage above 5 cc. has proven useIess and refractory. If additional quantities are indicated in continued hemorrhage or hemophiliacs, it is better to aIIow a time Iapse of two hours or more between doses. In this way the beneficial effects from this therapy may be proIonged for days or weeks. AI1 statisticat reports as we11 as our experience have shown that this drug has caused material reduction in clotting and bIeeding time in nearly a11 cases. This reduction occurs whether cIotting and bIeeding times are normal or abnormal initiaIIy. How this result is accomplished has not been explained fuIIy, as there are stiI1 unsoIved factors in the clotting mechanism of brood.

CLINICAL

MATERIAL

AND

RESULTS

At the Passaic Genera1 Hospital the foIIowing data were obtained from case records of the past eleven years where koagamin was administered: 542 cases of tonsihectomy and adenoidectomy ; * twenty-five cases of genera1 surgery (incIuding twenty-three cases of peIvic, or gahbladder and biIe duct surgery). RecentIy a check series of tweIve cases, mostly general surgery, was done against tweIve control cases in which koagamin was not used. (TabIes I and II.) In this series it wiI1 be noted that in the contro1 patients bIeeding time was increased an average of 41 per cent and coaguIation time was increased an average of 16 per cent one hour after operation. However, in those patients receiving koagamin the bIeeding time was reduced an average of 13 per cent and the coagulation time was decreased an average of 23 per cent one hour after operation. From our figures it is cIear that in evaluating the tota effect of koagamin we must aIso consider the increase in bIeeding and cIotting time caused by operation atone. We strongIy suspect * These were uniformIy satisfactory from the standpoint of minima1 bkeding. (About one case a year presented a probIem of abnorma1 oozing.) Series of Dr. L. M. Matthews.

Control

of Hemorrhage TABLE

EFFECT

OF KOAGAMIN

I

IN TWELVE

SljRGlCAL

CASES

Bleeding

Time

CoaguIation

Time

3’15” 6’00” 5’1o” 3’05” 5’15” 5’10” 3’30” 3’30”

3’oo” 3’IV” 3’0”” 2’30”

I Case and Date Admitted

I

Operation Before Operation

One Hour after

Operation ~~~.~~_.

E. C., ro/17/53 E. B., ro/2r/53 C. L., 10/22/53 A. L., lo/24153 B. B., 1r/19/53 M. B., 1r/17/53 M. T., 1r/17/53 B. W., 1r/19/53 T. D., ’ l/24/53 B. P., 1r/24/53 1. N., 12/l/53 J. R., 12/l/$3

ChoIecystectomy Hysterectomy Hernia BiIateraI hernia Postoperative adhesions Incision of foot drainage Hysterectomy Hernia Hernia ChoIecystectomy Fistula of anus, hemorrhoidectomy Orchiopexy

I’I

0’30” 0’30” 0’45” 0145”

j"

I’d 1’00” ‘00” ‘00” 0’30” 0’45” 0’45” 0’30” 0’45” 0’30” 0’3”” I

I’I$”

I

0’45”

1’00”

~

0’30” 0’30” 0’45” 0’30” 0’30”

5‘35”

~ 3’00” 2’45”

3’00”

3'10"

3'00"

4'45"

4'15'1

4'45"

3'00"

3'15"

2’4jf1

23% average decrease

L3 ?;, average decrease

-

TABLE STUDIES

IN TWELVE

II

SURGICAL

CONTROLS*

Bleeding Time (:ase and Date Admitted

G. B., A. w., D.

B.,

ill. N.,

I 1/2/5x

1I /2/53 II/I3/53

I l/13/53

A.%

11/13/53

B.C.,

11/17/53

E.

T.,

C.L

11!19/53 11/19/53

D.C.,

11/19/53

W. N., I I /19/53 N. i%., 11/24/53 B. S., 12/2/53

Operation Before Operation

Saphenous ligation Cyst of breast Diagnostic diIatation and curettage Hysterectomy Hernia GangIion of wrist Dilatation and curettage Abdominal tumor and ovarian cyst Tumor of thigh Hernia ChoIecystectomy PiIonidal cyst

One Hour after Operation

007

Time

3ne Hour after 3peration

Before Operation

5'00"

j'O0"

4'00"

4'00"

1’00”

4'30"

4'4j"

1’30” I ‘00”

3'30"

j'30"

3'10"

4'45"

I’d

3'15"

4,'30"

5'00"

j'I0"

4'00"

5'00"

4'00"

4'35l'

I ‘00”

0’30” 1’45” I ‘00” 1’30”

0’45”

1'15"

4 1%

* Did not receive koagamin.

I

Coagulation

1’15” 0’30“ 1’30”

1’00” 0’30” 1’30” 0’30” 0’45” 0’30” “‘45” 0’30” 1’30” 0’30”

! I

I

average Increase

$‘OO“

5’00”

3'00"

3'00"

3'30"

4t45'i 16%

average increase

Control

of Hemorrhage 4. DORMAN,N. H. TransurethraI

that inhalant anesthetics may pIay a roIe in this increase. If this method is followed, the average reduced percentages caused by koagamin are: bIeeding time, 44 per cent; clotting time, 39 per cent.

5.

6. 7.

CONCLUSIONS

8.

In view of the extensive work done by others and our own series of cases as summarized herein, representing the prophyIactic as we11 as the therapeutic vaIue of koagamin,* I beIieve that the folIowing conclusions are justified: I. Koagamin has a unique blood-clotting faculty, acting promptIy and usuaIIy requiring 0nIy one or two injections. 2. It is fuIIy compatible with vitamin K where it is indicated. 3. If given promptIy and judiciously, it wiI1 often obviate the use of transfusion and avoid waste of precious bIood so often required. 1. Its prophyIactic use preoperativeIy tends to reduce bIood loss and to facilitate surgical procedures. 3. Where genera1 oozing occurs as in tonsiIlectomx, peIvic surgery, breast amputation and prostatrc surgery, it is particuIarIy vaIuabIe. 6. Over an eIeven-year period no untoward effects have been observed with the use of koagamin in 567 cases.

9.

10.

‘949. MARTIN, G. J. The mechanism of the action of dicarboxylic acids in blood coagulation. Am. J. Pbysiol., 130: 574, 1940. 12. MCGAVACK, T. H. Some recent advances in the treatment of hemophilia. M. Clin. North America, 24: 791, 1940. 13. MEAD, S. V. Control of hemorrhage. Am. J. Ortbodontics, 26: 982, 1940. ‘4. MILLIKEY, L. F. The use of a new blood coagulant in transurethra1 prostatic resection. J. Ural., Ij.

16.

’ 7. 18.

19. 20.

REFERENCES I. BLAIN, A. W. and CAMPBELL, K.

N. Hemostatic effect of oxaIic acid. Arch. Surg., 44: I I 17, 1942. 2. COPLEY, A. D. and LALICH, J. J. The influence of blood transfusion and injections of bursa pastoris (shepherd’s_purse) extract on the cIot resistance in two hemophiliacs. Am. J. M. SC., 204: 665,

1I. PersonaI communication,

her 7, 1943. * hlanufactured by Chatham Newark, N. J.

Pharmaceuticals,

‘94.1. LINN, B. F. Sublingual application of a solution of oxaIic and malonic acids to decrease cIotting time in ora surgery. J. Am. Dent. A., 38: 168,

II.

Acknowledgment: I wish to express my thanks to the personne1 of the Passaic General Hospital laboratory and others, who assisted in the preparation of this paper.

’ 942. 3. CUTLER, hl.

prostatic resection: a statistica study based on 300 consecutive cases. J. Ural., 45: 41 I, 1941. FEDER, J. M. Some modern concepts of oral pathoIogy. South. Med. tV Surg., 105: IO, 1943. HERBST, W. P. and WEINSTEIN, J. J. Observations of the action of koagamin. J. urol., 5 I : 325, 1944. HOLLENDER, A. R. Offrce Treatment of the Nose, Throat and Ear. Chicago, 1943. Year Book PubIisher, Inc. HULSE, W. F. ControI of hemorrhage. Arch. Otohryng., 37: 831, 1943. JACKSON, A. S. The use of oxaIic acid in the treatment of hemorrhage. Jackson Clin. Bull., 3: 7-13,

42: 75. ‘939. PAGE, R. C. et aI. Effect of oxaIic acid intravenously on bIood-coaguIation time in three hemophiliacs. Ann. Int. Med., 14: 78, 1940. QUICK, A. J. Macy Foundation Conference on Blood Clotting and AIIied ProbIems, vo1. 2, pp. 202-218, 1949. SCAFFLE, K. PuImonary hemorrhage. South. Med. &’ &T&, 103: 5, 1941. SCHUMANN,E. A. Newer concepts of brood coagulation and the contro1 of hemorrhage. Am. J. Oh. fY Cynec., 38: 1002, 1939. SCHUMANN, E. A. Benign uterine hemorrhage in nonpregant women. Am. J. Surg., 48: 353, 1940. STEINBERG, A. and BROWN, W. R. A new concept regarding the mechanism of cIotting and the contro1 of hemorrhage. Am. J. Pbysioi., 126: 638,

1939. 21. STEINBERG, A. et al. The role of oxalic acid and certain reIated di-carboxyIic acids in the treatment and contro1 of hemorrhage. Ann. Otol., Rbin. @TLuryng., 49: 1008, 1940. 22. STOKES, J. H. et al. Modern CIinicaI Syphilology, 3rd ed., PhiIadeIphia, 1944. W. B. Saunders Co. with new etioIogir 23. \\'OLl:E,hl. ;21. Rhinophyma: and therapeutic considerations. Luryngoscope,

NovrmInc.,

53: 172, 1943.

908