• 1

    Arocha-Piñango CL, 1967. Fibrinolysis caused by contact with caterpillars: preliminary communication. Acta Cient Venez 18 :136–139.

  • 2

    Kelen EM, Picarelli ZP, Duarte AC, 1995. Hemorrhagic syndrome induced by contact with caterpillars of the genus Lonomia (Saturniidae, Hemileucinae). J Toxicol Toxin Rev 14 :283–308.

    • Search Google Scholar
    • Export Citation
  • 3

    Duarte AC, Caovilla J, Lorini I, Lorini D, Montovani G, Sumida J, Marifre PC, Silveira R, 1990. Insuficiência renal aguda por acidentes com lagartas. J Bras Nefrol 12 :184–186.

    • Search Google Scholar
    • Export Citation
  • 4

    Burdmann EA, Antunes I, Saldanha LB, Abdulkader RC, 1996. Severe acute renal failure induced by the venom of Lonomia caterpillars. Clin Nephrol 46 :337–339.

    • Search Google Scholar
    • Export Citation
  • 5

    Donato JL, Moreno RA, Hyslop S, Duarte A, Antunes E, Le Bonniec BF, Rendu F, Nucci G, 1998. Lonomia obliqua caterpillar spicules trigger human blood coagulation via activation of factor X and prothrombin. Thromb Haemost 79 :539–542.

    • Search Google Scholar
    • Export Citation
  • 6

    Veiga AB, Pinto AFM, Guimarães JA, 2003. Fibrinogenolytic and procoagulant activities in the hemorrhagic syndrome caused by Lonomia obliqua caterpillars. Thromb Res 111 :95–101.

    • Search Google Scholar
    • Export Citation
  • 7

    Pinto AF, Dobrovolski R, Veiga AB, Guimarães JA, 2004. Lonofibrase, a novel α-fibrinogenase from Lonomia obliqua caterpillars. Thromb Res 113 :147–154.

    • Search Google Scholar
    • Export Citation
  • 8

    Seibert CS, Shinohara EM, Sano-Martins IS, 2003. In vitro hemolytic activity of Lonomia obliqua caterpillar bristle extract on human and Wistar rat erythrocytes. Toxicon 41 :831–839.

    • Search Google Scholar
    • Export Citation
  • 9

    Fraiha Neto H, Costa Jr DC, de Leão RN, Ballarini AJ, 1992. Acidentes hemorrágicos por larvas de Lonomia. Schvartsman S, ed. Plantas Venenosas e Animais Peçonhentos. Sao Paulo: Sarvier, 241–244.

  • 10

    Fan HW, Duarte AC, 2003. Acidentes por Lonomia. Cardoso JL, França FO, Fan HW, Malaque CM, Haddad V Jr., eds. Animais Peçonhentos no Brasil. Biologia, Clínica e Terapêutica dos Acidentes. Sao Paulo: Sarvier/FAPESP, 224–232.

  • 11

    Zannin M, Lourenço DM, Motta G, Dalla Costa LR, Grando M, Gamborgi GP, Noguti MA, Chudzinski-Tavassi AM, 2003. Blood coagulation and fibrinolytic factors in 105 patients with hemorrhagic syndrome caused by accidental contact with Lonomia obliqua caterpillar in Santa Catarina, southern Brazil. Thromb Haemost 89 :355–364.

    • Search Google Scholar
    • Export Citation
  • 12

    Bick RL, Baker WF, 1992. Disseminated intravascular coagulation syndromes. Hematol Pathol 6 :1–24.

  • 13

    Rakic S, 1999. New findings on the physiopathology of acute hemolytic transfusion reaction. Med Pregl 52 :19–24.

  • 14

    Brady HR, Brenner BM, Lieberthal W, 1996. Acute renal failure. Brenner BM, ed. The Kidney. Fifth edition. Philadelphia: W. B. Saunders Company, 1200–1252.

Past two years Past Year Past 30 Days
Abstract Views 0 0 0
Full Text Views 130 115 9
PDF Downloads 57 39 1
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 

 

 

A CASE OF HEMOLYSIS RESULTING FROM CONTACT WITH A LONOMIA CATERPILLAR IN SOUTHERN BRAZIL

CEILA M. S. MALAQUEIntensive Care Unit, Emílio Ribas Institute of Infectology, São Paulo, Brazil; Butantan Institute, São Paulo, Brazil; Department of Nephrology, Laboratory of Basic Research, University of São Paulo School of Medicine, São Paulo, Brazil

Search for other papers by CEILA M. S. MALAQUE in
Current site
Google Scholar
PubMed
Close
,
LÚCIA ANDRADEIntensive Care Unit, Emílio Ribas Institute of Infectology, São Paulo, Brazil; Butantan Institute, São Paulo, Brazil; Department of Nephrology, Laboratory of Basic Research, University of São Paulo School of Medicine, São Paulo, Brazil

Search for other papers by LÚCIA ANDRADE in
Current site
Google Scholar
PubMed
Close
,
GERALDINE MADALOSSOIntensive Care Unit, Emílio Ribas Institute of Infectology, São Paulo, Brazil; Butantan Institute, São Paulo, Brazil; Department of Nephrology, Laboratory of Basic Research, University of São Paulo School of Medicine, São Paulo, Brazil

Search for other papers by GERALDINE MADALOSSO in
Current site
Google Scholar
PubMed
Close
,
SANDRA TOMYIntensive Care Unit, Emílio Ribas Institute of Infectology, São Paulo, Brazil; Butantan Institute, São Paulo, Brazil; Department of Nephrology, Laboratory of Basic Research, University of São Paulo School of Medicine, São Paulo, Brazil

Search for other papers by SANDRA TOMY in
Current site
Google Scholar
PubMed
Close
,
FLÁVIO L. TAVARESIntensive Care Unit, Emílio Ribas Institute of Infectology, São Paulo, Brazil; Butantan Institute, São Paulo, Brazil; Department of Nephrology, Laboratory of Basic Research, University of São Paulo School of Medicine, São Paulo, Brazil

Search for other papers by FLÁVIO L. TAVARES in
Current site
Google Scholar
PubMed
Close
, and
ANTONIO C. SEGUROIntensive Care Unit, Emílio Ribas Institute of Infectology, São Paulo, Brazil; Butantan Institute, São Paulo, Brazil; Department of Nephrology, Laboratory of Basic Research, University of São Paulo School of Medicine, São Paulo, Brazil

Search for other papers by ANTONIO C. SEGURO in
Current site
Google Scholar
PubMed
Close

Contact with a caterpillar of the genus Lonomia can result in a hemorrhagic syndrome. Lonomia obliqua venom activates prothrombin and factor X and promotes fibrinogenolytic activity. Although crude L. obliqua bristle extract can induce hemolytic activity in human and rat erythrocytes, there have been no reports of hemolysis in the cases of human contact. We report a confirmed human case of Lonomia venom-induced hemolysis.

Contact with a caterpillar of the genus Lonomia can result in a hemorrhagic syndrome. This was first described in 1967 by Arocha-Piñango in a case in Venezuela.1 In Brazil, the risk of Lonomia envenomation was considered low until 1989, when a high number of human cases were reported in southern Brazil. In 2004, 364 cases were reported in Brazil. The patients had a hemorrhagic syndrome after skin contact with Lonomia obliqua. Two species of the genus Lonomia are known to cause hemorrhagic syndrome: L. achelous, which is found in Venezuela and northern Brazil, and L. obliqua, which is found in southern Brazil. The symptoms of envenomation typically begin with a burning sensation at the point of contact, followed by erythema and edema. The skin around the site is warm to the touch. Headache, general discomfort, nausea, and vomiting may also occur. The hemorrhagic phenomena may appear as soon as 1 hour after contact or up to 12 hours later. Ecchymoses and hematomas are often seen and may be accompanied by bleeding from various sites. The bleeding is occasionally severe enough to be life threatening. Some patients with hemostatic disorders can develop acute renal failure (ARF).24 The L. obliqua venom activates both prothrombin and factor X and promotes fibrinogenolytic activity.57 Crude L. obliqua bristle extract has been shown to induce hemolytic activity in human and rat erythrocytes.8 However, there have been no reports of hemolysis in the cases of human contact. We report a confirmed human case of Lonomia venom-induced hemolysis.

A 64-year-old man accidentally came into contact with a caterpillar. Immediately after contact, he experienced burning pain, edema, and erythema at the site of contact (on his right hand). Subsequently, he began vomiting and developed a headache. Eight hours after the accident, he developed hematemesis, bleeding gums, and hematuria. Twenty-four hours after contact (day 1), he sought treatment and was admitted to a hospital where a saline infusion was administered. Laboratory testing showed a hemoglobin level = 11.9 g/dL, hematocrit = 36%, 17,800 leukocytes/mL, 57,000/platelets/mL, serum urea = 137 mg/dL, serum creatinine = 4.6 mg/dL, total bilirubin = 2.6 mg/dL, indirect bilirubin = 2.1 mg/dL, thrombin time = 22.8 seconds, international normalized ratio = 3.54; and activated partial thromboplastin time = 50 seconds. Based on these results, he was diagnosed with caterpillar contact-induced hemorrhagic syndrome accompanied by ARF.

On day 2, he was transferred to Emílio Ribas Institute of Infectology in Sao Paulo, Brazil. Upon admission, he showed dehydration and jaundice, and his blood pressure was 160/90 mmHg. There was mild edema and erythema in his right hand, without ecchymoses or other bleeding. Laboratory tests showed a hemoglobin level = 9.3 g/dL, hematocrit = 26.6%; urea = 197 mg/dL, serum creatinine = 6.4 mg/dL, fibrinogen = 0.06 g/L, fibrin degradation products = 640 μg/mL, D-dimer = 256 μg/mL, and lactate dehydrogenase = 5,028 mg/dL. He received a specific antivenom (antilonomic serum; Butantan Institute, Sao Paulo, Brazil) and renal replacement therapy was started. Twenty-four hours after receiving the antivenom, the patient showed a significant improvement in coagulation test results: fibrinogen increased to 1.41 g/L, fibrin degradation products decreased to 320 μg/mL, and D-dimer levels decreased to 16 μg/mL.

Despite the improvement in the coagulation test results and no further signs of hemorrhage, there was a significant decrease in hemoglobin levels (to 5.1 g/dL on the fourth post-incident day), and the patient showed lower platelet levels (18,000/mm3). We suspected hemolysis because the patient had higher serum levels of indirect bilirubin and lactate dehydrogenase (LDH) at admission. Hemolysis was confirmed by the observed levels of serum haptoglobin (10 mg/dL), and plasma free hemoglobin (1,220 mg/L) (Table 1).

On day 20, creatinine levels began to decrease, and hemodialysis was discontinued. By day 25, the patient had significantly lower levels of creatinine and urea (5.6 mg/dL and 91 mg/dL, respectively), and although not considered completely recovered, he was discharged. In a follow-up examination on day 30, a normal creatinine level (1.5 mg/dL) was observed. To rule out possible an underlying predisposition for hemolysis we obtained the following test results: hemoglobin electrophoresis: HbA1 97.4% (normal range = 94.5–98.5%), HbA2 1.6% (normal range = 1.5–3.5%), HbF 1.1% (normal value < 2), HbS absent, glucose-6-phosphate dehydrogenase = 177 mU/10 erythrocytes (normal value = 131 ± 13), haptoglobin = 90 mg/dL (normal range = 30–200); LDH = 390 U/L (normal range = 240–480). Tests results for Heinz bodies and for sucrose were negative. Results of a Ham test and a Coombs test were negative.

The clinical course after Lonomia accident is probably related to the intensity of the contact, the particular larvae stage, and the type of immediate medical treatment provided.9,10 The bleeding syndrome may begin as soon as within a few hours or up to several days after the accident and can be severe enough to be life threatening.2 Early laboratory coagulation tests invariably showed prolonged prothrombin times, activated partial thromboplastin times and thrombin times, various degrees of hypofibrinogenemia, and typically normal or slightly decreased platelet counts.11 We report a proven case of hemolysis resulting from a Lonomia accident. The patient had intravascular hemolysis, as evidenced by low plasma levels of haptoglobin, high levels of free hemoglobin, and high serum levels of LDH. In addition, serum levels of unconjugated bilirubin were increased. In experimental studies performed in Wistar rats, it has been demonstrated that intravascular hemolysis and hemoglobinuria occur after exposure to Lonomia venom (Oliveira MRL and others, unpublished data). It has been shown that crude L. obliqua bristle extract has indirect and direct hemolytic effects on human and rat erythrocytes.8 In the same study it was shown that bristle extracts of L. obliqua caterpillars possess at least two components capable of lysing human and rat erythrocyte membranes in vitro. One has a phospholipase effect that lyses erythrocytes in the presence of lecithin. The other can destroy the erythrocyte membrane structure, possibly through a proteolytic effect.

One interesting feature of this case was the extremely low platelet count. In a study of coagulation and fibrinolytic factors in 105 patients who had accidental contact with L. obliqua caterpillars, Zannin and others observed significant thrombin production, intense consumption of fibrinogen, and high production of D-dimer, indicating a disseminated intravascular coagulation (DIC) process.11 Platelet counts were within normal ranges in most of the L. obliqua-envenomed patients studied. Only nine patients had (slight) reductions in their platelet counts.11 We believe that cases with significantly reduced levels of platelets are likely associated with hemolysis-induced DIC. A frank hemolytic transfusion reaction is unquestionably a triggering event for DIC. However, hemolysis of any etiology may trigger DIC. Lysed erythrocytes act as partial thromboplastin reagent in the intrinsic reactions, leading to generation of prothrombin activator (Factor Xa). They do so in an unusual way in that they can bypass the surface activation steps of the intrinsic mechanism.12 Cytokines may also play an important role in the development of DIC-related hemolysis.13

A remarkable feature in this case was the rapid development of severe anuric ARF after venom inoculation. Surprisingly, despite the fact that this patient was treated with hemodialysis for 24 days, he did not completely recover renal function until 1 month after the accident. We did not perform a renal biopsy on this patient. It is therefore likely that he had developed acute tubular necrosis. The etiology of ARF is multifactorial. Although this patient never developed hemodynamic instability, he did had severe hemorrhagic syndrome. Hemolysis is another leading cause of acute tubular necrosis.14 Hemolysis-related ARF is caused by hemoglobin, which is highly nephrotoxic, especially in volume-depleted patients. We cannot rule out a direct nephrotoxic effect of the venom. Another possible explanation for the ARF might be massive DIC-related deposition of microthrombi in glomeruli. However, although most of the patients in the study conducted by Zannin and others11 developed severe coagulopathy with pronounced fibrinogen reduction, none had renal failure. We can postulate that among the many possible causes of ARF, the etiology of the present case was hemolysis-related acute tubular necrosis or hemolysis-related DIC.

In conclusion, although Lonomia-induced hemolysis has previously been reported in an animal model, the case herein reported represents the first confirmed instance of such hemolysis in a human patient.

Table 1

Summary of laboratory findings*

Post-incident day
Parameter 1 2 3 4 5 6 10 25 Normal
* LDH = lactate dehydrogenase; TB/IB = total bilirubin/indirect bilirubin; PTT = partial thromboplastin time (activated); PT = prothrombin time; PA = prothrombin activity; FDP = fibrin degradation products.
Hemoglobin 11.9 9.3 8.3 5.1 8.9 8.4 8.0 8.6 12–16 g/dL
Hematocrit 36 26.6 22.9 15 26 25 24 25 37–42%
Platelets 57,000 45,000 18,000 34,000 34,000 68,000 252,000 280,000 150–400 × 103/mm3
Urea 137 197 157 169 110 136 160 91 7–50 mg/dL
Creatinine 4.6 6.4 7.1 6.4 4.3 6.5 8.4 5.6 0.6–1.3 mg/dL
LDH 5,028 6,960 3,234 2,463 2,426 1,422 120–360 U/L
TB/IB 2.6/2.1 1.0/0.7 0.8/0.6 0.7/0.5 0.9/0.4 0.2–1.0 mg/dL
PTT 50 50.9 31.2 24.6 23.6 20.3 27.6 25–37 sec
PT 22.8 18 11.9 12 11.7 10.8 11.1 12–16 sec
PA 35 44 127 99 115 179 125 70–100%
Reticulocyte count 0.4 1.6 1.4 5.9 0.5–1.5%
Fibrinogen 0.06 1.41 2.05–2.59 g/L
FDP 640 320 < 2.5 μg/mL
D-dimer 256 16 0.5 μg/mL
Haptoglobin 10 13 30–200 mg/dL
Free hemoglobin 1,220 830 < 50 mg/L

*

Address correspondence to Ceila M. S. Malaque, Instituro Butantan, Hospital Vital Brazil, Av. Vital Brazil 1500, Sao Paulo, SP, Brazil, 05503-900. E-mail: cmalaque@uol.com.br

Author’s addresses: Ceila M. S. Malaque and Geraldine Madalosso, Instituto Butantan, Hospital Vital Brazil, Av. Vital Brazil 1500, Sao Paulo, SP, Brazil, 05503-900, Telephone: 55-11-3726-7962, E-mail: cmalaque@uol.com.br. Lúcia Andrade and Antonio C. Seguro, Disciplina de Nefrologia, Faculdade de Medicina da Universidade de Sao Paulo, Av. Dr. Arnaldo, 455, Terceiro Andar, Sala 3310, Sao Paulo, Brazil, 01246-903, Telephone: 55-11-3066-7281, Fax: 55-11-3088-2267. Sandra Tomy and Flávio L. Tavares, Laboratório de Fisiopatologia, Instituto Butantan, Av. Vital Brazil 1500, Sao Paulo, SP, Brazil, 05503-900, Telephone: 55-11-3726-7222 extension 2163.

Acknowledgments: We thank the intensive care staff at Emílio Ribas Institute of Infectology for excellent assistance and patient care. We also thank Jefferson Davis Boyles for correcting the English and style of the manuscript.

REFERENCES

  • 1

    Arocha-Piñango CL, 1967. Fibrinolysis caused by contact with caterpillars: preliminary communication. Acta Cient Venez 18 :136–139.

  • 2

    Kelen EM, Picarelli ZP, Duarte AC, 1995. Hemorrhagic syndrome induced by contact with caterpillars of the genus Lonomia (Saturniidae, Hemileucinae). J Toxicol Toxin Rev 14 :283–308.

    • Search Google Scholar
    • Export Citation
  • 3

    Duarte AC, Caovilla J, Lorini I, Lorini D, Montovani G, Sumida J, Marifre PC, Silveira R, 1990. Insuficiência renal aguda por acidentes com lagartas. J Bras Nefrol 12 :184–186.

    • Search Google Scholar
    • Export Citation
  • 4

    Burdmann EA, Antunes I, Saldanha LB, Abdulkader RC, 1996. Severe acute renal failure induced by the venom of Lonomia caterpillars. Clin Nephrol 46 :337–339.

    • Search Google Scholar
    • Export Citation
  • 5

    Donato JL, Moreno RA, Hyslop S, Duarte A, Antunes E, Le Bonniec BF, Rendu F, Nucci G, 1998. Lonomia obliqua caterpillar spicules trigger human blood coagulation via activation of factor X and prothrombin. Thromb Haemost 79 :539–542.

    • Search Google Scholar
    • Export Citation
  • 6

    Veiga AB, Pinto AFM, Guimarães JA, 2003. Fibrinogenolytic and procoagulant activities in the hemorrhagic syndrome caused by Lonomia obliqua caterpillars. Thromb Res 111 :95–101.

    • Search Google Scholar
    • Export Citation
  • 7

    Pinto AF, Dobrovolski R, Veiga AB, Guimarães JA, 2004. Lonofibrase, a novel α-fibrinogenase from Lonomia obliqua caterpillars. Thromb Res 113 :147–154.

    • Search Google Scholar
    • Export Citation
  • 8

    Seibert CS, Shinohara EM, Sano-Martins IS, 2003. In vitro hemolytic activity of Lonomia obliqua caterpillar bristle extract on human and Wistar rat erythrocytes. Toxicon 41 :831–839.

    • Search Google Scholar
    • Export Citation
  • 9

    Fraiha Neto H, Costa Jr DC, de Leão RN, Ballarini AJ, 1992. Acidentes hemorrágicos por larvas de Lonomia. Schvartsman S, ed. Plantas Venenosas e Animais Peçonhentos. Sao Paulo: Sarvier, 241–244.

  • 10

    Fan HW, Duarte AC, 2003. Acidentes por Lonomia. Cardoso JL, França FO, Fan HW, Malaque CM, Haddad V Jr., eds. Animais Peçonhentos no Brasil. Biologia, Clínica e Terapêutica dos Acidentes. Sao Paulo: Sarvier/FAPESP, 224–232.

  • 11

    Zannin M, Lourenço DM, Motta G, Dalla Costa LR, Grando M, Gamborgi GP, Noguti MA, Chudzinski-Tavassi AM, 2003. Blood coagulation and fibrinolytic factors in 105 patients with hemorrhagic syndrome caused by accidental contact with Lonomia obliqua caterpillar in Santa Catarina, southern Brazil. Thromb Haemost 89 :355–364.

    • Search Google Scholar
    • Export Citation
  • 12

    Bick RL, Baker WF, 1992. Disseminated intravascular coagulation syndromes. Hematol Pathol 6 :1–24.

  • 13

    Rakic S, 1999. New findings on the physiopathology of acute hemolytic transfusion reaction. Med Pregl 52 :19–24.

  • 14

    Brady HR, Brenner BM, Lieberthal W, 1996. Acute renal failure. Brenner BM, ed. The Kidney. Fifth edition. Philadelphia: W. B. Saunders Company, 1200–1252.

Author Notes

Reprint requests: Ceila M. S. Malaque, Instituto Butantan, Hospital Vital Brazil, Av. Vital Brazil 1500, Sao Paulo, SP, Brazil, 05503-900.
Save