Practice CMAJ•JAMC

Practice CMAJ•JAMC Teaching cases Key points Caterpillar-induced bleeding syndrome in a returning • A complete history, including rel- evant travel history, is key to diag- nosing the patient’s condition. traveller • As adventure travel becomes more popular, more cases of exposure to The case: A 22-year-old woman who She had no lymphadenopathy. Re- exotic diseases will be encoun- was previously healthy presented sults of her cardiovascular, respiratory tered. with a 4-day history of expanding and abdominal examinations were • Management strategies must in- ecchymoses. She had no other bleed- unremarkable. There was no evi- clude rapid recognition and collab- oration with experienced clinicians ing manifestations and denied any dence of physical trauma, but she had to facilitate specialized treatment constitutional symptoms, myalgias, extensive ecchymoses on both legs protocols. arthralgias or rashes. Her medical (Figure 1). • Online searches can be central to history was unremarkable. She was Seven days before admission our patient management. not taking any medication, and she patient had returned from northeast- had no family history of bleeding ern Peru, where she had stepped problems or hematologic disorders. barefoot on 5 caterpillars. Immedi- walked. A headache also developed. Her last normal menstrual period was ately after contact with the caterpil- Both the foot pain and headache re- 2 weeks before admission. lars, she experienced burning pain in solved over the subsequent 12 hours On examination, our patient was her foot, radiating proximally to her and she did not seek medical care at DOI:10.1503/cmaj.071844 afebrile and had normal vital signs. thigh. The pain worsened when she that time. Results of initial laboratory tests are summarized in Table 1. We diag- nosed an atypical presentation of disseminated intravascular coagulation or primary fibrinolysis triggered by an unknown process. We started treatment with fresh frozen plasma, cryo- precipitate and fibrinogen concentrate. In view of her presenting signs and symptoms and travel history, we searched MEDLINE and Google Scholar, which revealed the possibility of caterpillar envenomation that could account for all her clinical symptoms and laboratory results. Although our local poison control centre had no knowledge of caterpillar envenomation, they facilitated contact with clinicians from Brazil, who recommended immediate administration of a locally produced antivenin. They recommended that we avoid treatment with blood products (fresh frozen plasma and cryo- precipitate) because they felt these could worsen the coagulation abnormalities. We made arrangements to obtain the antivenin from Brazil, which took 48 hours to arrive. Our patient’s condition remained Photos courtesy of Mike Knash stable for the initial 48 hours. On her Figure 1: Extensive ecchymoses on our patient’s legs 2 days after admission. third day in hospital (10th day after envenomation), alveolar hemorrhage, 158 CMAJ • JULY 15, 2008 • 179(2) © 2008 Canadian Medical Association or its licensors Practice anuric acute kidney injury and hemo- to humans. However, caterpillar- dynamic instability developed. She re- induced bleeding syndrome is a unique ceived mechanical ventilation, vaso- reaction specific to caterpillars of the active agents and continuous renal Lonomia genus, a type of moth native to replacement therapy. Her hemato- South America (Figure 2). In a 5-year logic and coagulation abnormalities period, there were 688 cases of caterpil- worsened, and there was evidence of lar envenomation reported in the state progressive microangiopathic hemo- of Rio Grande do Sul in Brazil.2 lytic anemia, consumptive thrombocy- Caterpillar-induced bleeding syn- topenia and disseminated intravascu- drome is characterized by a consump- lar coagulation. She was treated with tion of clotting factors induced by the Photo courtesy of Roberto Pinto Moraes (Butantan Institute) fibrinogen concentrate, aprotinin and caterpillar’s venom. Initial symptoms Figure 2: Photograph of Lonomia washed packed red blood cells and are usually mild, consisting of local obliqua. Note the aposematic coloration. platelets. We received the antivenin burning pain, headache, nausea and from Brazil and administered it on the vomiting.1,3 As clotting factors are con- 10th day after envenomation (third sumed through venom-induced activa- rhage, acute renal failure and intracra- day in hospital); however, our pa- tion of the coagulation system, bleed- nial hemorrhage.5,6 tient’s organ dysfunction progressed, ing manifestations, such as mucosal Generally, patients with this syn- and she died of multiorgan failure hemorrhages, hematuria and ecchymo- drome have normal platelet and hemo- later that day. sis, become evident from 1 hour to globin levels, minimal hemolysis and 10 days after envenomation. Abnormal red blood cell fragmentation, and nor- clotting parameters include prolonged mal levels of factors II, VII, IX, X, XI, Caterpillar envenomation occurs after prothrombin, partial thromboplastin XII and antithrombin. Rarely, clinically contact with the bristles of spiny cater- and thrombin times, low to undetect- significant hemolysis has also been re- pillars, which induces symptoms rang- able fibrinogen levels with increased ported.7 These characteristics, particu- ing from mild cutaneous reactions to se- fibrinogen degradation products, ele- larly the normal platelet count, are not vere systemic reactions.1 Twelve vated D-dimer levels and absence of in- consistent with classic disseminated families of caterpillars worldwide have hibitors.1,3,4 Complications of Lonomia intravascular coagulation and suggest a been identified as potentially hazardous envenomation include alveolar hemor- unique mechanism of clotting derange- ment, including fibrinolysis. Two species of Lonomia caterpillars Table 1: Results of initial laboratory tests performed for a 22-year-old woman who are known to cause this bleeding syn- presented with a 4-day history of expanding ecchymoses drome.1,6 L. obliqua is native to south- ern Brazil, and L. achelous is more Test Result (reference range) commonly found in Venezuela and Hemoglobin, g/L 125 (120–160) northern Brazil. Both caterpillars in- Platelet count, x 109/L 216 (140–450) duce a consumptive coagulopathy and Leukocyte count, x 109/L 7.9 (4.0–11.0) bleeding syndrome that is similar in presentation. Although the pathophysi- Haptoglobin, mg/L 610 (650–1900) ologic processes involved are not com- μ Total bilirubin, mol/L 16 (< 20) pletely known, the mechanism by Lactate dehydrogenase, U/L 180 (100–225) which this bleeding syndrome occurs is Creatinine, μmol/L 65 (40–115) slightly different depending on which International normalized ratio 5.3 (0.8–1.2) species caused it. Partial thromboplastin time, s 105 (27–40) Two procoagulant toxins have been identified in the venom of L. obliqua.1,6 Fibrinogen, g/L < 0.20 (2.2–4.2) Losac is an activator of factor X, and D-dimer, ng/mL FEU > 4000 (< 500) Lopap is an activator of prothrombin. 1:1 mixing of patientís plasma with Showed correction, consistent with The mechanism of L. obliqua-induced normal pooled plasma absence of an inhibitor bleeding syndrome is a consequence of Coagulation factor II, U/mL 0.56 (0.50–1.50) systemic intravascular activation of co- Coagulation factor V, U/mL 0.50 (0.50–1.50) agulation, which leads to a consump- Coagulation factor XIII, U/mL 0.14 (0.60–1.69) tive coagulopathy and secondary fibri- Peripheral blood smear No morphologic evidence of hemolysis nolysis in which the extent of Human chorionic gonadotropin, U/L < 5 (< 5) fibrinogen depletion correlates with the severity of bleeding manifestations. Pelvic ultrasound Normal The procoagulant and anticoagulant Note: FEU = fibrinogen equivalent units. activity1,3,6 of the toxins identified in the CMAJ • JULY 15, 2008 • 179(2) 159 Practice Coagulation cascade (clot formation) Factor X (inactive) Upstream activation of the coagulation + Prothrombin cascade Lonomin III (not discussed here) + Factor Xa + Lonomin IV + Factor V + Fibrinogen + Lonomin VIa – Thrombin + Fibrinolytic pathway (clot dissolution) Fibrin Lonomin VIi Factor XIIIa + – Lonomin V Cross-linked fibrin Lonomin II – – Plasmin Plasminogen + Lonomin I and V Fibrin degradation products, D-dimers Figure 3: Caterpillar-induced bleeding syndrome results from exposure to the venom of the Lonomia genus caterpillars. Toxins (lonomins) in the venom of Lonomia achelous caterpillars cause an activation of the coagulation system. This ultimately consumes clotting factors and leads to systemic bleeding manifestations and abnormal clotting parameters, low fibrinogen levels and increased fibrin degradation. + = promotion of activity, – = inhibition of activity/degradation. venom of L. achelous is described in are more common with L. achelous than tions of bleeding and acute renal fail- Figure 3. Lonomin II and lonomin I ac- with L. obliqua.1,6 Decreased plasmino- ure. Current recommendations include tivate fibrinolysis, and lonomin V is a gen, α2-antiplasmin and protein C levels treatment with purified fibrinogen con- factor XIII protease. There is also a have also been documented.1 centrates, antifibrinolytics and timely mild disseminated intravascular coagu- Traditionally, patients were treated administration of the antivenin.1,3,6 This lation with L. achelous envenomation with fresh frozen plasma and cryopre- course of action usually results in rapid that is attributable to procoagulant ac- cipitate. However, management

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