Consumption coagulopathy caused by a boomslang bite: A case report

THROMBOSIS RESEARCH Printed in the United

vo1.3, PP. Pergamon

States

173-182, 1973 Press, Inc.

CONSUMPTION COAGULOPATHY CAUSED BY A BOOMSLANG BITE A CASE REPORT

Georg Matell, Dag Nyman ,,Birgitta Werner and Soren Wilhelmsson, Dept. of Medicine, Sodersjukhuset, the Swedish Poison Information Centre and the Blood Coagulation Laboratory, Karolinska Sjukhuset, Stockholm, Sweden

(Received 8.5.1973; Accepted by

in revised Editor H.C.

form 9.6.1973. Godal)

ABSTRACT Coagulation disturbances in a man bitten by the South African snake Dispholidus typus (boomslang) are reported, The patient developed consumption coagulopathy with secondary fibrinolysis, Beside the coagulation disturbances, hemolysis with hemoglobinuria and a transient impairment of the renal function were noted, Heparin treatment together with whole blood and plasma substitution resulted in an improvement of the condition, Administration of specific antivenom normalized completely all the coagulation factors,

INTRODUCTION Dispholidus typus (boomslang) is a snake normally living in South Africa, It is non-aggresive, belonging to the back-fanged group, The bites are followed by bleeding symptoms (1, 2), mostly due to consumption coagulopathy (3,4), Below is reported the clinical course of a patient bitten by a boomslang and the coagulation analysis performed before and after the administration of a specific antivenom, 173

17’1

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MATERIALS AND METHODS Blood for coagulation studies was taken into polystyrene centrifuge tubes as described previously.(5), 0.13 M trisodium citrate was used as anticoagulant. Fibrinogen was determined according to Bergstrbm et al, (6), but the -thrombin concentration was 400 NIH units/ml, Prothrombin, factor V, factor

VII, factor VIII, factor IX, factor X,

factor XI and factor XII were determined according to previously described methods (6,7,8,9,10,11), Plasminogen, alfa-2-macroglobulin and antithrombin III

were determined

with the quantitative radial imnunodiffusion technique of Mancini using specific antisera (12). Fibrinogen Degradation Products (FDP) were determined with the hemagglutination inhibition test of Merskey (13). All the chemical laboratory tests were performed according to the Standard procedures used at Sbdersjukhuset, Stockholm, CASE REPORT A 27-year-old male was admitted to Stidersjukhuseton March 27, 1972, having been bitten by a boomslang 17 hours previously. He worked at a mobile terrarium, Before the bite he had consumed alcohol, At the bite both fangs penetrated the skin in the right thenar region, Initially he was well but went to another institution where he was given hydrocortisone, 300 mg, intravenously and released, Twelwe hours following the bite, the patient noted bleeding from the gums, nose and the site of the bite, his urine was red and he was brought to Sbdersjukhuset, On admission, the patient was markedly diaphoretic, No respiratory disturbances were noted, His mental functions were normal, The blood pressure was 170/90, pulse 72 and regular, Profuse bleeding was noted from the nose, gums and the site of the bite, The patient's urine was grossly bloody, Physical examination was otherwise negative or non-contributory, Relevant laboratory findings are shown in Tables I,

II and III,

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TABLE I Chemical Analysis Concerning Hemolysis and Liver Function,

Hapto- LUH ,H;;e';Hb g "b glogin, uni;s bite mg L 18

12,7

-

30

10.4

10

78

6.4

-

126

10.4

150

10.4

673

Bilirubin, mg % -

GOT, units -

GPT, units

Alkaline Albuphosphatase min, units g% -

-

Hb ur7ne g"x

4.3

0.5

3.6

1,O

3,0

24

611

1.3

22

40

4.2

3.4

0,'

-

-

1.1

12

44

4,2

3.8

0

-

594

1,'

16

48

3,4

3.5

0 0

Normal 13-

509

loo-

0,2-

a-

B-

2-

3,8-

values 17

150

250

1,2

35

35

9

5.2

TABLE II Chemical Analysis Concerning Renal Function and Electrolyte Balance,

Hours after bite

Creatinine, wi %

Na_ mequ/l

K, mequ/l

C', mequ/l

Bicarbonate, mequ/l

mequ”

Urinary flow, ml/24 h

Ca

B

18

2.0

140

2,7

107

24

4.0

2200

30

1.7

137

3.0

90

32

4.7

3300

78

1.7

138

2.5

82

40

-

2200

126

0,9

140

2,2

99

28

-

1800

150

0.7

138

2.7

101

28

-

2200

Normal

0.9-

1370

3,6-

990

210

4,3-

values

1.3

150

5.2

110

25

5.2

Fibri-

nogen

g %

0

0.05

0.10

0.22

1.55

1.88

0,25-

0.35

Hours

after

bite

24

40

64

71

87

111

Normal

values

130

650

121

56

.34

26

21

11

activ,

%

II

130

65-

160

108

58

37

28

25

activ.

%

V

130

65-

100

105

100

100

87

96

activ,

91

VII

130

65-

158

145

148

74

52

51

activ,

%

VIII

65130

65130

65

82 103

58

95

119

82

63

56

activ.

%

X

98

100

activ.

#

IX

130

65-

108

88*

76

90

112

104

activ,

x

XI

130

65-

124

108

72

76

104

activ,

%

XII

120

70-

88

73

76

62

normal

% of

AT III

Coagulation Parameters Determined During the Course

TABLE III

120

5

70-

44

46

44

-

31

70

-

176

352

pg/ml

0.35

0,25-

0.30

0.20

0.14

0.14

0.14

0.23

mg/ml

nogen

300

150-

128

80

52

62

61

153

lox3

let

FDP Plasmi- Plate-

36

38

50

normal

% of

a2-M

0 & bJ r G

?

2

z $

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BITE

The patient was treated with redcell concentrate, fresh frozen plasma, fibrinogen and AHF containing 1,6 to 1,7 g of fibrinogen per 100 ml (Fig, 1). factor activity % of normal 160 -

ant ivcnom administration

IL0 120100. 8060. factor VUl dOfactor V

20.

factor II

Oplatelets fibrinogen

?? 103

gY. -

160-

1.6 -

140-

l.L-

120.

1.2.

loo-

1.0.

80.

0.8.

60.

0.6.

LO-

0.4.

20-

0.2.

o-

o.oa

3-o

i

6-O

40

Ii0 hours after bite

Fibrinogen

II

IiLyII

AHF Freshly frozen plasma Heparin

FIG, 1 Coagulation parameters in relation to antivenom administration and blood substitution, The amount of fibrinogen administered through the factor VIIIconcentrate (1.6 - 1.7 g per 100 ml) has been added, Fibrinogen: 1 block = 1 g* AHF: 1 block = about 300 U, Freshly frozen plasma: 1 block = 200 ml,

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Within 3 - 4 hours after admission, the profuse bleedings slowed notably. Macroscopic hematuria disappeared within 10 hours after admission, though microscopic hematuria remained for one week, 13 hours following admission, the platelet count dropped from 153000 to 61000 (Fig, 1). Heparin therapy 200 U/kg body-weight/24 hours as a continuous intravenous infusion was begun (Fig, 1). After the coagulation factors had normalized the heparin dose was increased to 400 U/kg body-weight/24 hours (Fig, l), During his early course, the patient developed hemolysis and hemoglobulinuria (Table I), A transient and moderate rise in serum creatinine was noted, but good urine output was maintained (Table II), 500 ml of 15 % mannito1 and 6 g sodium bicarbonate per OS was administered over 24 hours, Marked hypokaliemia developed despite administration of 120 - 200 mequ of potassium chloride/24 hours, On the third hospital day transfusions were withheld and 69 hours after the bite anti-venom (Dispholidus typus anti-venom batch 0 0804)' 20 ml was given by slow intravenous injection, Test doses had first been administered intradermally and by conjunctival installation without adverse reaction, One hour following the injection, the patient developed melena and diffuse bleeding from the gums and skin, Blood pressure dropped to 90/35 and pulse was 130, After rapid transfusions of plasma and redcell concentrate the condition improved, 62 hours following admission (79 hours after the bite) all bleeding stopped, The further course was uneventful and the patient was discharged in good health on the 8th hospital day, DISCUSSION Earlier reports show that boomslang venom produces consumption coagulopathy (3, 4). The venom seems to convert prothrombin into thrombin by a direct action (4).

In our case we found low levels of factors II,

V and VIII

as well as an-

' Obtained from Dr. P, A. Christensen, South African Institute for Medical Research, Johannesburg,

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tithrombin

III

BY

BOOMSLANG

and platelets (Table III),

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The consumption of factors V and VIII

could be due to a direct activating effect of the venom on these factors, Thrombin, which is produced, could also cause an.,aggregationof the platelets which in turn would activate factors V and VIII, Degradation of the coagulation factor proteins by plasmin as well as a direct proteolytic effect of the venom must be considered as well. The direct proteolytic effect of the venom has been shown with high concentrations of the venom (4). The mechanisms discussed concerning factor V and VIII

may also lower factor X,

The fibrinolytic system is activated later in the course (Fig, Z), shown by decreased levels of alfa-2-macroglobulin and plasminogen, FDP are initially found in a high concentration with a gradual decrease later in the course, These findings are in correspondence with a secondary fibrinolysis initiated by the intravascular coagulation, However, the venom may cause a direct coagulation of fibrinogen resulting in a defect fibrin giving a high concentration of FDP and an increased bleeding tendency, Spies et al, (2) showed at autopsy that fibrin thrombi were found throughout the bodTa;er

boomslang bite, In our case only minor signs of impaired

microcirculation were noted shown by slightly impaired renal function early in the course, The essentially intact microcirculation could be due to the heparin therapy, Its use here , combined with factor replacement, was followed by a steady but slow increase of clotting factors and a more rapid decrease of clinical bleeding, It was, however, following administration of antivenom that the coagulation parameters returned rapidly to normal (Fig, 1). It is likely that the initial decrease in clinical bleeding was due to replacement therapy, but that coagulation factors remained depressed despite heparin because of circulating venom, Administration of specific antivenom would then have removed the initial cause of the intravascular coagulation allowing heparin to work, The dose of heparin was maintained at a relatively low level because of the bleeding risk since the patient had both hypofibrinogenemia and thrombocytopenia, Because of the risk of fibrin deposits in various organs heparin therapy was continued after the disappearance of the consumption coagulopathy in order to prevent thronbotic complications, The untoward reaction to the antivenom injection may have been coincidental, On that day transfusion had been withheld, but the possibility of an allergic or a toxic reaction increasing the intravascular coagulation must be considered, This is suggested by the transient decrease of factor X and platelets

(Table III),

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antivenom administration l-l

plasminogcn m9%

0.3

-

0.2

-

0.1

-

o.oo<2-macroglobulin % 70. 6050LO30.

loO, 0

I 30

60

I)0 hours after

1 120 bile

FIG, 2 Fibrinolytic parameters during the course.

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Renal and hepatic dysfunction have been reported as cornnOn complications of boomslang bites (2, 3), As mentioned above, early in the course increased serum creatinine levels suggest decreased renal function, This could, however, be the result of an increased breakdown of the muscle tissue, The impaired renal function reported previously could be due to an insufficient microcirculation produced by intravascular coagulation, Hemoglobin deposits in the renal tubules

have also been reported

(2, 3). In our case we found both hemo-

lysis and hemoglobinuria (Table I) but the urinary flow was excellent throughout the course, No signs of acute tubular necrosis were noted, This could be prevented by high diuresis and bicarbonate administration in addition to heparin therapy, ACKNOWLEDGEMENTS The authors wish to express their sincere gratitude for invaluable help during the various stages of treatment of this case to Drs, Birger Blomback and Margareta BlombYck, Coagulation Laboratory, Dr, Mandagan Tim, Statens Bakteriologiska Laboratorium, Stockholm, Dr, Carl Edelstam, Naturhistoriska Museet, Stockholm and for handy assistance in the preparation of this manuscript to Miss Lena Wikbladh and Miss Ulla Martin, REFERENCES 1,

FITZ SIMMS, F, W, The snakes of Southern Africa, T, Maskew Miller: p, 141, 1919,

2,

SPIES, S, K,, MALHERBE, L, F, and PEPLER, W, S, Boomslang bite with afibrinogenemia, Description of a case with necropsy findings, S, Afr, Med. J,: 36, 834, 1962,

3,

LUKIER, J, B, and FRITZ, V, U, Consumptive coagulopathy caused by a boomslang bite, S, Afr, Med, J,: 43, 1052, 1969,

4,

MACKAY, N,, FERGUSON, J, C,, BUGSHARVE, A,, FORRESTER, A, T, T, and MCNICOL, G, P, The venom of the boomslang (Dispholidus typus-):In vivo and in vitro studies, Thromb, Diath, Haemorrh,: 2l, 234, 1969,

5,

BLOMBXK, M,, NDREN, I, and SENNING, A, Coagulation disturbances during extracorporeal circulation and the postoperative period, Acta Clin, Stand,: l27, 433, 1964,

6,

BERGSTRUM, K,, BLOMBXK, B, and KLEEN, G, Studies on the plasma fibrin0' lytic activity in a case of liver cirrhosis, Acta Med, Stand,: 168, 291, 1960,

7,

NOREN, I, Specific assay of prothrombin, A method using a freeze-dried reagent of intrinsic coagulation factors, Stand, J, clin, Lab, Invest: 25, 47, 1970,

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WOLF, P, A modificationfor routine laboratoryuse of Stefanini'smethod of estimating factor V activity in human oxalated plasma, J, Clin, Pathol,:2, 34, 1953, M, and von FRANCKEN, I, On an inherited autosomal haemorrhagicdiathesis with antihemophilicglobulin (AHG) deficiency and prolonged bleeding time, Acta Med, Stand,: 159, 35, 1957,

NILSSON, I.-M,, BLOMBXK,

10,

NILSSON, I.-M., BLOMBACK,M,, RAMGREN, 0, and von FRANCKEN, I, Haemophilia in Sweden II, Carries of haemophiliaA and B, Acta Med. Stand,: 17'1,223, 1962,

11,

BACHMANN, F,, DUCKERT, P, and KOLLER, F, The Stuart-Prowerfactor assay and its clinical significance,Thromb, Diathes, Haemorrh,:1, 24, 1958,

12,

MANCINI, G,, CARBONATA,A, 0, and HEREMANS, J, F, Immunochemicalquantitation of antigens by single radial immunodiffusion,Immunochemistry: 2, 235, 1965,

13,

MERSKEY, C,, LALEZARI, P, and JOHNSON, A, J, A rapid simple sensitive method for measuring fibrinolytic split products in human serum, Proc, Sot, Exp. Biol,: 131, 871, 1969,